Immunoliposomes As a Promising Antiviral Agent against SARS-CoV-2.

According to the World Health Organization, as of January 3, 2020 to September 13, 2023, there were approximately 23 million confirmed cases of COVID-19 reported in the Russian Federation, about 400 thousand of which were fatal. Considering the high rate of mutation of the RNA-containing virus genome, which inevitably leads to the emergence of new infectious strains (Eris and Pyrola), the search for medicinal antiviral agents remains an urgent task. Moreover, taking into account the actively mutating receptor-binding domain, this task requires fundamentally new solutions. This study proposes a candidate immunoliposomal drug that targets the S protein of SARS-CoV-2 by the monoclonal neutralizing antibody P4A1 and ensures the penetration of a highly active ribonuclease into the virus-infected cell, which degrades, among cellular RNA, viral RNA too. We demonstrate a more than 40-fold increase in the neutralizing activity of the developed drug compared to the free monoclonal neutralizing antibody.

An ELISA Platform for the Quantitative Analysis of SARS-CoV-2 RBD-neutralizing Antibodies As an Alternative to Monitoring of the Virus-Neutralizing Activity.

Monitoring of the level of the virus-neutralizing activity of serum immunoglobulins ensures that one can reliably assess the effectiveness of any protection against the SARS-CoV-2 infection. For SARS-CoV-2, the RBD-ACE2 neutralizing activity of sera is almost equivalent to the virus-neutralizing activity of their antibodies and can be used to assess the level of SARS-CoV-2 neutralizing antibodies. We are proposing an ELISA platform for performing a quantitative analysis of SARS-CoV-2 RBD-neutralizing antibodies, as an alternative to the monitoring of the virus-neutralizing activity using pseudovirus or "live" virus assays. The advantage of the developed platform is that it can be adapted to newly emerging virus variants in a very short time (1-2 weeks) and, thereby, provide quantitative data on the activity of SARS-CoV-2 RBD-neutralizing antibodies. The developed platform can be used to (1) study herd immunity to SARS-CoV-2, (2) monitor the effectiveness of the vaccination drive (revaccination) in a population, and (3) select potential donors of immune plasma. The protective properties of the humoral immune response in hospitalized patients and outpatients, as well as after prophylaxis with the two most popular SARS-CoV-2 vaccines in Russia, were studied in detail using this platform. The highest RBD-neutralizing activity was observed in the group of hospitalized patients. The protective effect in the group of individuals vaccinated with Gam-COVID-Vac vaccine was 25% higher than that in outpatients and almost four times higher than that in individuals vaccinated with the CoviVac vaccine.

[Airway stenting in patients with complex benign tracheobronchial stenosis]. / Odnomomentnoe endoprotezirovanie trakhei i glavnykh bronkhov pri rubtsovom stenoze.

Tracheal and bronchial stenting is actively used for cancer and benign airway stenosis. This procedure is common in patients with advanced cancer. Stenting ensures breathing and availability of early chemo- and radiotherapy without the need for tracheostomy. This procedure is less common in patients with benign tracheal stenosis. In this case, isolated tracheal or bronchial stenting is performed. Complex tracheobronchial stenosis is extremely rare and creates significant difficulties. We present 3 cases of tracheobronchial stenting for cicatricial stenosis. In each case, stenosis was dilated with a rigid bronchoscope or balloon dilatation. Then, a silicone stent was installed. Resection with an appropriate anastomosis was contraindicated due to advanced pathological process. Thus stenting was regarded as a palliative operation. The follow-up periods were 9 months, 3 and 10 years. Each patient underwent inhalation therapy, endoscopy and repeated stenting if necessary.

[Surgery of primary tracheal tumors]. / Khirurgiya pervichnykh opukholei trakhei.

OBJECTIVE: To determine the main forms of primary tracheal cancer (PTC), to specify the indications for various surgeries in these patients depending on extent and localization of lesion. MATERIAL AND METHODS: There were 263 PTC patients. Benign tumors were diagnosed in 68 (25.9%) patients, malignancies - in 195 (74.1%) cases. Tracheal cancer includes 3 basic morphological variants - adenocystic cancer (49.7%), carcinoid (18.7%) and squamous cell carcinoma (19.0%). Other forms of malignancies were much less common. We applied endoscopic intraluminal and open surgeries. In malignant PTC, open surgeries were performed in 165 (84.6%) out of 195 patients. Baseline palliative endoscopic treatment was performed in 30 patients. They underwent airway recanalization (with subsequent tracheal stenting in 19 patients). Endoscopic resection was preferred for benign tumors. RESULTS: Twenty (12.1%) patients died after open surgery, and 1 (3.3%) patient died after endoscopic procedure. Most lethal outcomes occurred in early years of development of tracheal surgery. The causes of mortality were tracheal anastomotic failure in 12 patients, pneumonia in 6 patients, and arterial bleeding in 2 patients. Severe postoperative period was observed in all 3 patients after tracheal replacement with a silicone prosthesis. Long-term treatment outcomes depended on morphological structure of PTC. Favorable results were observed in patients with neuroendocrine tumor (carcinoid), worse outcomes in adenocystic cancer and unfavorable results in squamous cell carcinoma (p<0.0013). Five-year survival rates were 75%, 65.6%, and 13.3%; 10-year survival rates were 75%, 56.2%, and 13.3%, respectively. These outcomes after combined treatment of primary tracheal cancer were significantly better compared to lung cancer (p<0.05 when compared to global data). CONCLUSION: Treatment of primary tracheal cancer should be based on classical principles of modern oncology (combined therapy, tumor resection with lymphadenectomy). Open and endoscopic interventions are justified. PTC is characterized by more favorable outcomes compared to lung cancer. It is difficult to analyze long-term results in tracheal cancer depending on various features of tumor process due to small number of observations. Accurate conclusions require multiple-center studies, preferably with international participation, which can convincingly prove certain concept.

Horses as a source of bioactive fecal strains Enterococcus mundtii.

Bacteriocin-producing bacteria with probiotic character are known as nutritional supplements mainly for livestock. Among those beneficial bacteria we also found enterococci. Because the species strains Enterococcus mundtii also can produce bacteriocins, this study was focused on fecal strains E. mundtii from horses and their bioactivity with a view to their possible future use in breeding. Rectal removal from 47 horses (40 mares and 7 stallions), the Norik breed from Murán were sampled in eastern Slovakia during November 2019 year. Horses age ranged from five months up to 23 years. Using MALDI-TOF mass spectrometry and 16S rRNA sequences analysis, 14 strains were allotted to the species E. mundtii. Bacteriocin substances produced by the strains EMKD 38/1, EMKD 40/2, EMKD 34/2 and EMKD 41/3 showed inhibitory activity against the most susceptible (principal) indicator strain Enterococcus avium EA5 and against listeriae as well (inhibitory activity from 100 up to 1 600 AU/mL). Only strain EMKD 41/3 possess Ent P and Mundticin KS genes and showed the broadest inhibitory activity. Ent B gene possessing strain EMKD 24/1 inhibited a growth of only indicator strain EA5. Identified E. mundtii tolerate low pH 3 and oxgall/bile. They were hemolysis, gelatinase and DNase negative and mostly susceptible to clinical antibiotics which are properties requested for application potential of strain. Substance from the strain with the broadest antimicrobial spectrum showed its practical/application potential, e.g. for optimizing the host microbiota which is important regarding the maintenance of animal`s health status.

Enterocin Ent7420 and sage application as feed additives for broiler rabbits to improve meat carcass parameters and amino acid profile.

The effect of enterocin (Ent)7420 and sage on rabbit meat carcass quality and amino acid (AA) conetnt was evaluated. Ninty-six Hyla male rabbits (35 days aged) were divided into experimental: E (Ent7420), S (sage), E + S (Ent7420 + sage) and control (C) groups. The additives were administrated in drinking water during 21 days. Time and time and treatment interaction effect were noted on carcass traits. The highest protein level was noted in rabbits LTL receiving Ent7420 in combination with sage. Essential (EAA) and non-essential amino acid (NEAA) levels increased in all experimental groups, with the highest EAAs in group E + S (E + S vs. E, S: P < 0.01; E + S, E, S vs. C: P < 0.001) and NEAAs in group E (E vs. S, E + S, C: P < 0.001). The dietary inclusion of Ent7420 alone and in combination with sage can improve the rabbit meat quality due to its higher protein, EAAs and NEAAs profile.

[Airway complications after lung transplantation]. / Bronkhial'nye oslozhneniya posle transplantatsii legkikh.

Lung transplantations have been regularly performed in the Russian Federation since 2010. Therefore, the number of lung transplant recipients, as well as the number of patients with airway complications following lung transplantation has been increasing. Treatment of these patients takes place not only in transplantation centers, but also in other hospitals. This review is devoted to risk factors, clinical manifestations, treatment and prevention of airway complications after lung transplantation. We analyzed literature data over the last 15 years. It was confirmed that bronchoscopy is a «gold standard¼ for diagnosis of airway complications while bronchoscopic interventions are preferred for treatment. Balloon and rigid bronchodilation and endoscopic airway stenting are the most effective interventions. Silicone stents are the most optimal. Antimicrobial prophylaxis and timely use of antiproliferative immunosuppressive drugs are important factors in prevention and treatment of airway complications after lung transplantation.

Enterocins as Novel Feed Additives in Rabbit Diet: Enterocin Ent M and Durancin Ent ED26E/7, Their Combination, and Effects on Microbiota, Caecal Fermentation, and Enzymatic Activity.

The present study investigates the effects of enterocin Ent M and durancin Ent ED26E/7 applied separately and in combination on the intestinal microbiota, caecal enzymatic activity, and fermentaion of rabbits. Eighty rabbits (M91 meatline, aged 5 weeks, both sexes) were divided into groups E (Ent M; 50 µL/animal/day), D (Ent ED26E/7; 50 µL/animal/day), E + D (Ent M + Ent ED26E/7), and control (C). The additives were administered in drinking water for 21 days. Antimicrobial activity of Ent M and Ent ED26E/7 on coliforms (E, E + D: P < 0.001) and pseudomonads (D: P < 0.05) in feces was noted, compared to C. Ent M and Ent ED26E/7 application stimulated caecal enzymatic activity in rabbits. Pectinolytic (E vs. D, E + D: P < 0.01), inulolytic (E vs. E + D: P < 0.01; E vs. C: P < 0.05), and amylolytic (E vs. D, E + D. P < 0.001; E vs. C: P < 0.01) activities were influenced by Ent M, while cellulolytic (D vs. E + D: P < 0.01) and inulolytic (D vs. E + D, C: P < 0.01) activities by Ent ED26E/7 treatment. The cellulolytic and pectinolytic acitivities changed with time. Treatment × time interaction was detected for cellulose and xylan degradation. During Ent M and Ent ED26E/7 treatment, increased ammonia, lactic, butyric and iso-valeric acid, and lower acetic, propionic, iso-butyric, valeric, and caproic acid concentrations were noted. It can be concluded that Ent M and Ent ED26E/7 application can improve rabbit health due to reduced spoilage microbiota and enhanced caecal enzymatic activity.

COVID-19 in Russia: Clinical and Immunological Features of the First-Wave Patients.

The coronavirus disease outbreak in 2019 (COVID-19) has now achieved the level of a global pandemic and affected more than 100 million people on all five continents and caused over 2 million deaths. Russia is, needless to say, among the countries affected by SARS-CoV-2, and its health authorities have mobilized significant efforts and resources to fight the disease. The paper presents the result of a functional analysis of 155 patients in the Moscow Region who were examined at the Central Clinical Hospital of the Russian Academy of Sciences during the first wave of the pandemic (February-July, 2020). The inclusion criteria were a positive PCR test and typical, computed tomographic findings of viral pneumonia in the form of ground-glass opacities. A clinical correlation analysis was performed in four groups of patients: (1) those who were not on mechanical ventilation, (2) those who were on mechanical ventilation, and (3) those who subsequently recovered or (4) died. The correlation analysis also considered confounding comorbidities (diabetes, metabolic syndrome, hypertension, etc.). The immunological status of the patients was examined (levels of immunoglobulins of the M, A, G classes and their subclasses, as well as the total immunoglobulin level) using an original SARS-CoV-2 antibody ELISA kit. The ELISA kit was developed using linear S-protein RBD-SD1 and NTD fragments, as well as the N-protein, as antigens. These antigens were produced in the prokaryotic E. coli system. Recombinant RBD produced in the eukaryotic CHO system (RBD CHO) was used as an antigen representing conformational RBD epitopes. The immunoglobulin A level was found to be the earliest serological criterion for the development of a SARS-CoV-2 infection and it yielded the best sensitivity and diagnostic significance of ELISA compared to that of class M immunoglobulin. We demonstrated that the seroconversion rate of "early" N-protein-specific IgM and IgA antibodies is comparable to that of antibodies specific to RBD conformational epitopes. At the same time, seroconversion of SARS-CoV-2 N-protein-specific class G immunoglobulins was significantly faster compared to that of other specific antibodies. Our findings suggest that the strong immunogenicity of the RBD fragment is for the most part associated with its conformational epitopes, while the linear RBD and NTD epitopes have the least immunogenicity. An analysis of the occurrence rate of SARS-CoV-2-specific immunoglobulins of different classes revealed that RBD- and N-specific antibodies should be evaluated in parallel to improve the sensitivity of ELISA. An analysis of the immunoglobulin subclass distribution in sera of seropositive patients revealed uniform induction of N-protein-specific IgG subclasses G1-G4 and IgA subclasses A1-A2 in groups of patients with varying severity of COVID-19. In the case of the S-protein, G1, G3, and A1 were the main subclasses of antibodies involved in the immune response.

Sublingual administration of 5-aminolevulinic acid for laser-induced photodiagnostics and photodynamic therapy of oral cavity and larynx cancers.

BACKGROUND: The study aimed to develop a method for sublingual administration of 5-aminolevulinic acid to patients and evaluate its effectiveness in fluorescence diagnostics and photodynamic therapy of neoplasms of the oral cavity and larynx. METHODS: The boundaries of the neoplasms were established by the video-fluorescence diagnostics and clarified using spectral-fluorescent diagnosis before and after photodynamic therapy. RESULTS: The fluorescence diagnostics demonstrated a high accumulation of protoporphyrin IX, induced by sublingual administration of 5-aminolevulinic acid to patients before the photodynamic therapy and photobleaching of protoporphyrin IX in pathologically altered tissues after the photodynamic therapy. Glucose contained in the sublingual dose supports active transport of 5-ALA into the cells. It increases the PpIX accumulation in the cells, therefore improving the PD and PDT efficacy. CONCLUSION: The study and the initially obtained results demonstrated the possibility and effectiveness of laser-induced photodiagnostics and photodynamic therapy with sublingual administration of 5-ALA to patients with premalignant lesions of the oral cavity and larynx. It can eliminate the threat of the transformation of these diseases into malignant tumors and prevent the need for surgical treatment.

Erythropoietin as an independent prognostic factor in myelodysplastic syndromes.

AIM: To assess the level of erythropoietin (EPO) in blood sera of patients with different subtypes of myelodysplastic syndromes (MDS) from different risk subgroups and to determine its prognostic role. MATERIALS AND METHODS: EPO was measured by enzyme-linked immunosorbent assay in peripheral blood of 54 patients with different MDS subtypes according to the French-American-British (FAB) classification. The comparison group consisted of 15 healthy individuals. Complete blood count (hemoglobin, leukocyte and platelet levels) was determined and bone marrow cells were characterized morphologically. The overall and leukemia-free survivals were estimated by Kaplan - Meier method. RESULTS: The level of ЕРО in MDS was reliably higher in comparison with healthy persons (p < 0.01, Mann - Whitney test). No statistically significant difference was found in serum EPO concentration between the groups of patients with low- and high-risk MDS (603.5 pg/ml vs 721.0 pg/ml; p > 0.05). In transfusion-dependent patients, the level of EPO was significantly higher than in other patients, which may be due to increased endogenous EPO secretion resulting from chronic hypoxia. A negative correlation was revealed between EPO level and Hb level as well as between EPO level and percentage of blast cells in bone marrow in high-risk MDS patients but not in patients with less aggressive variants of MDS. Instead, patients with low-risk MDS had a negative relationship between concentrations of EPO and tumor necrosis factor alpha (p = 0.06, Kendall's tau test). No significant difference was found between EPO concentration in cases differing by bone marrow cellularity or the presence of cytogenetic abnormalities. An EPO concentration below 200 pg/ml was a predictor of shorter overall survival in patients with all MDS subtypes (p < 0.05, Mann - Whitney test). In patients with all FAB disease subtypes, there was no relationship between the leukemia-free survival and serum EPO concentration. CONCLUSION: This study shows that lower serum EPO level may be considered as one of the additional adverse prognostic factors in MDS patients.

[Assessment of tracheal elasticity and tracheal anastomosis tension in cicatricial stenosis]. / Otsenka elastichnosti trakhei i natyazheniya trakheal'nogo anastomoza pri rubtsovom stenoze.

OBJECTIVE: To assess the tracheal elasticity and tracheal anastomosis tension for prevention of anastomosis-related complications and estimation of the maximum length of resection. MATERIAL AND METHODS: At the first stage, 20 patients with cicatricial tracheal stenosis underwent tracheoscopy in usual position, under maximum flexion and extension of the head for the period from September 2017 to December 2019. We measured the total length of trachea and length of stenotic segment. Tracheal extensibility was assessed considering the difference in measurements. At the second stage, anastomosis tension was intraoperatively measured using a dynamometer in normal head position, as well as at maximum flexion in 22 patients who underwent tracheal resection. Unlike multiple other studies, we studied tissue tension intraoperatively. RESULTS: Mean length of trachea was 12.8 cm, extensibility - 1.3 cm. Tracheal elasticity was greater in patients with a longer trachea and in patients under 40 years old. Mean length of resection was 3.9 cm (30% of mean length of trachea), anastomosis tension - 2.7 H or 270 g. Head flexion was followed by tension decrease by 0.7 H (26.9%), i.e. 70 g. This approach is less effective in case of resection of more than 30% of trachea length in a particular patient. CONCLUSION: Further experience in measurement of tracheal extensibility and anastomosis tension will make it possible to establish clinical significance of these indicators for prevention of complications.

Characterisation of Faecal Staphylococci from Roe Deer (Capreolus capreolus) and Red Deer (Cervus elaphus) and Their Susceptibility to Gallidermin.

Our current knowledge of microbiota in wild ruminants is limited. The goal of this study was to evaluate staphylococcal species in red and roe deer for various attributes (haemolysis, DNase, and urease activities; lactic acid and biofilm production; and antibiotic profile) and their susceptibility to gallidermin. Sixteen staphylococcal strains were identified from faeces of 21 free-living animals (9 adult female Cervus elaphus-red deer and 12 young female Capreolus capreolus-roe deer) sampled by the Polish colleagues in the Strzalowo Forest District, Piska Primaeval Forest. The variability in the species of staphylococci was determined. Seven species (Staphylococcus capitis, S. epidermidis, S. haemolyticus, S. hominis, S. pseudintermedius, S. vitulinus and S. warneri) and five clusters/groups of coagulase-negative staphylococci (CoNS) were identified. The strains were generally not haemolytic and Dnase negative; did not form biofilms or only produced low-grade biofilms; exhibited high levels of lactic acid; were urease positive; and were generally susceptible to antibiotics (only two strains were resistant to multiple antibiotics). However, all of the strains were susceptible to the lantibiotic bacteriocin gallidermin, with a minimal inhibitory concentration of 0.0156 µg (up to 6400 AU/ml in arbitrary units). This is the first study to perform a detailed study of the properties of CoNS from roe and red deer.

Enterocin M and Sage Supplementation in Post-weaning Rabbits: Effects on Growth Performance, Caecal Microbiota, Fermentation and Enzymatic Activity.

The effects of enterocin (Ent) M and sage extract applied separately and in combination were investigated. EntM (E 50 µL/animal/day in water) and sage extract (S 10 µL/animal/day in water) were applied individually and in combination (E+S) to rabbits during 21 days of treatment. The rabbits' growth was not significantly influenced by the additives. Lower feed conversion (FC) was noted in the experimental groups compared with controls, with the lowest data detected in E. The antimicrobial activity of EntM was noted (in E+S: lactic acid bacteria-P < 0.01; in E, E+S: enterococci, enterobacteria-P > 0.05; in E: clostridia-P > 0.05). The most significant changes in fermentation between weaned and older rabbits were noted in amylolytic activity at day 21 (E P < 0.05; E + S P < 0.05); prolonged reduction effect of sage extract on amylolytic activity was observed. The activity of cellulase, pectinase and xylanase was higher in older than in younger animals. Decrease in lactic acid and volatile fatty acids was noted during EntM administration, with significant effect on propionic acid concentration (E P < 0.05; E+S P < 0.001). The sage extract reduced propionic acid (S P < 0.001) and butyric acid levels (S P < 0.05) and increased the concentrations of butyric, iso-valeric, valeric, caproic acids and lactic acid (P < 0.001). It seems to be that EntM and sage supplementation may improve the economy of rabbit farms (increased FC) and the health status of rabbits (reduction of spoilage microbiota, enhanced enzymatic activities in caecum).

Sensitivity to antimicrobials of faecal Buttiauxella spp. from roe and red deer (Capreolus capreolus, Cervus elaphus)detected with MALDI-TOF mass spectrometry.

Wild ruminants are an interesting topic for research because only limited information exists regarding their microbiota. They could also be an environmental reservoir of undesirable bacteria for other animals or humans. In this study faeces of the 21 free-living animals was sampled (9 Cervus elaphus-red deer, adult females, 12 Capreolus capreolus-roe deer, young females). They were culled by selective-reductive shooting during the winter season of 2014/2015 in the Strzalowo Forest District-Piska Primeval Forest (53° 36 min 43.56 sec N, 21° 30 min 58.68 sec E) in Poland. Buttiauxella sp. is a psychrotolerant, facultatively anaerobic, Gram-negative rod anaerobic bacte- rial species belonging to the Phylum Proteobacteria, Class Gammaproteobacteria, Order Entero- bacteriales, Family Enterobacteriacae and to Genus Buttiauxella. Buttiauxella sp. has never previ- ously been reported in wild ruminants. In this study, identification, antimicrobial profile and sensitivity to enterocins of Buttiauxella strains were studied as a contribution to the microbiota of wild animals, but also to extend knowledge regarding the antimicrobial spectrum of enterocins. Five strains were identified using the MALDI-TOF identification system (evaluation score value was up to 2.224) and allotted to the genus Buttiauxella including the species Buttiauxella gaviniae, B. ferragutiae, B. agrestis. Strains were DNase negative, and they hydrolysed esculin; fermentation of L-arabinose, D-mannitol and D-mannose was positive. Dulcitol, inositol reaction, urea and indol were negative. Buttiauxella strains did not form biofilm. They were resistant to at least one of the 13 antibiotics tested. B. agrestis 2/109/1 was resistant to amdinocillin, clindamycin and pen- icillin. However, Buttiauxella strains were sensitive to the enterocins used (inhibition activity ranged from 100 to 25 600 AU/ml).

[Immuno-PCR Assay for Quantitation of Antibodies to Epstein-Barr Virus].

Successful disease prevention and therapy critically depend on timely diagnosis of infections. Quantitative immuno-PCR (qiPCR) technology improves the sensitivity in the detection of antibodies to pathogens. A qiPCR-based assay was developed to determine IgG antibodies to Epstein-Barr virus (EBV) in the human blood serum. EBV nuclear protein 1 fragment (pEBV) was expressed in Escherichia coli. A synthetic single-stranded deoxyribonucleotide was conjugated to streptavidin, and the conjugate was used to detect рEBV-IgG1-biotin complexes by qiPCR. The IgG1 titers determined by qiPCR were compared to the results of enzyme-linked immunosorbent assay (ELISA). The sensitivity of qiPCR was one order of magnitude higher than that of ELISA. Thus, a highly sensitive qiPCR-based assay was developed to quantitate antibodies specific to the recombinant EBV antigen.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm: Volume 4.

Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortality.

Liver transplantations in Bulgaria--initial experience.

The filed of liver transplantation (LT) continues to evolve and is highly effective therapy for many patients with acute and chronic liver failure resulting from a variety of causes. Improvement of perioperative care, surgical technique and immunosuppression in recent years has led to its transformation into a safe and routine procedure with steadily improving results. The aim of this paper is to present the initial experience of the transplant team at Military Medical Academy - Sofia, Bulgaria. For the period of April 2007 - August 2014 the team performed 38 liver transplants in 37 patients (one retransplantation). Patients were followed up prospectively and retrospectively. In 36 (95%) patients a graft from a cadaveric donor was used and in two cases--a right liver grafts from live donor. The mean MELD score of the transplanted patients was 17 (9-40). The preferred surgical technique was "piggyback" with preservation of inferior vena cava in 33 (86%) of the cases and classical technique in 3 (8%) patients. The overall complication rate was 48%. Early mortality rate was 13% (5 patients). The overall 1- and 5-year survival is 81% and 77% respectivelly. The setting of a new LT program is a complex process which requires the effort and effective colaboration of a wide range of speciacialists (hepatologists, surgeons, anesthesiologists, psychologists, therapists, coordinators, etc.) and institutions. The good results are function of a proper selection of the donors and the recipients. Living donation is an alternative in the shortage of cadaveric donors.

Burst of succinate dehydrogenase and α-ketoglutarate dehydrogenase activity in concert with the expression of genes coding for respiratory chain proteins underlies short-term beneficial physiological stress in mitochondria.

Conditions for the realization in rats of moderate physiological stress (PHS) (30-120 min) were selected, which preferentially increase adaptive restorative processes without adverse responses typical of harmful stress (HST). The succinate dehydrogenase (SDH) and α-ketoglutarate dehydrogenase (KDH) activity and the formation of reactive oxygen species (ROS) in mitochondria were measured in lymphocytes by the cytobiochemical method, which detects the regulation of mitochondria in the organism with high sensitivity. These mitochondrial markers undergo an initial 10-20-fold burst of activity followed by a decrease to a level exceeding the quiescent state 2-3-fold by 120 min of PHS. By 30-60 min, the rise in SDH activity was greater than in KDH activity, while the activity of KDH prevailed over that of SDH by 120 min. The attenuation of SDH hyperactivity during PHS occurs by a mechanism other than oxaloacetate inhibition developed under HST. The dynamics of SDH and KDH activity corresponds to the known physiological replacement of adrenergic regulation by cholinergic during PHS, which is confirmed here by mitochondrial markers because their activity reflects these two types of nerve regulation, respectively. The domination of cholinergic regulation provides the overrestoration of expenditures for activity. In essence, this phenomenon corresponds to the training of the organism. It was first revealed in mitochondria after a single short-time stress episode. The burst of ROS formation was congruous with changes in SDH and KDH activity, as well as in ucp2 and cox3 expression, while the activity of SDH was inversely dependent on the expression of the gene of its catalytic subunit in the spleen. As the SDH activity enhanced, the expression of the succinate receptor decreased with subsequent dramatic rise when the activity was becoming lower. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaption and therapy.

Combined administration of bacteriocin-producing, probiotic strain Enterococcus faecium CCM7420 with Eleutherococcus senticosus and their effect in rabbits.

The effect of Enterococcus faecium CCM7420 (EF) - enterocin-producing and probiotic strain of rabbit origin, Eleutherococcus senticosus extract (ES) and their combination (ES+EF) was determined on selected bacteria in faeces and caecum content, leukocytes phagocytosis, blood biochemistry and growth performance. Ninety-six weaned rabbits were divided into 3 experimental (ES, EF, ES+EF) and control group (CG). The rabbits in the groups ES and EF+ES were fed commercial diet enriched with E. senticosus extract (30 g/100 kg feed), rabbits in groups EF and CG were fed untreated diet. The rabbits in the EF and ES+EF groups were administered with an overnight culture of E. faecium CCM7420 strain (500 microl/animal/day into water, 109 CFU/ml). The treatment period lasted 21 days. The microbiological examinations in faecal samples confirmed the presence of E. faecium CCM7420 strain. In groups EF and ES+EF, the reduction of faecal coliforms, Pseudomonas-like sp., Clostridium-like sp. and S. aureus was recorded. Leucocyte phagocytosis significantly increased in all experimental groups (P < 0.0001) compared to CG. The lowest GPx values were measured in the ES+EF group. Higher total protein, triglycerides and calcium concentrations were detected in experimental groups compared to CG. The cholesterol concentration decreased in the ES group. The highest average daily gain was recorded in EF group; in ES+EF the better feed conversion ratio and no mortality was recorded. These results indicated that the dietary supplementation with the E. faecium CCM7420 and E. senticosus extract stimulate the leukocytes phagocytosis and reduces the potential pathogens in rabbits digestive tract without oxidative stress and improve the growth performance.