[Infectious complications in acute period after traumatic brain injury]. / Infektsionnye oslozhneniya u patsientov v ostrom periode cherepno-mozgovoi travmy.

Patients with traumatic brain injury (TBI) are at high risk of infection. OBJECTIVE: To delineate infections in acute period of TBI, association between intracranial lesion type and risk of infection, as well as to estimate treatment outcomes in these patients depending on infection. MATERIAL AND METHODS: This study included 104 patients with TBI (80 men and 24 women) aged 33.01±14.35 years. All patients met the inclusion criteria: admission within 72 hours after TBI, age 18-75 years, ICU-stay >48 hours, available brain MRI data. Mild, moderate and severe TBI were diagnosed in 7%, 11% and 82% of patients, respectively. Analysis of infections was performed in accordance with the definitions of the Centers for Disease Control/National Healthcare Safety Network (CDC/NHSN). RESULTS: Acute period of TBI is associated with high incidence of infection (73%), and prevalent infection is pneumonia (58.7%). Severe intracranial damage in acute period of TBI (grade 4-8 according to MR-based classification by A.A. Potapov and N.E. Zakharova) is associated with higher incidence of infection. Infectious complications more than twice increase duration of mechanical ventilation, ICU- and hospital-stay. CONCLUSION: Infectious complications significantly affect treatment outcomes in acute period of TBI increasing duration of mechanical ventilation, ICU- and hospital-stay.

[Differential diagnosis of pneumonia as a complication of nasal liquorrhea in the context of the COVID-19 pandemic: Case report].

Nasal liquorrhea the outflow of cerebrospinal fluid from the cerebrospinal fluid spaces of the cranial cavity into the nasal cavity or paranasal sinuses due to the presence of a congenital or acquired defect in the bones of the skull base and meninges of various etiologies. Nasal liquorrhea leads to potentially fatal complications: meningitis, meningoencephalitis, pneumocephalus, brain abscess. Also, with nasal liquorrhea, less dangerous complications may occur: aspiration bronchopneumonia and gastritis. The article presents a case of aspiration pneumonia in two patients with nasal liquorrhea treated at the Burdenko National Medical Research Center for Neurosurgery during the COVID-19 pandemic. Both patients noted the profuse nature of the nasal liquorrhea, complained of coughing in a horizontal position. In both cases, no RNA virus (SARS-CoV-2) was detected during the polymerase chain reaction. Antibodies (IgG, M) to coronavirus were not detected. Computed tomography of the chest organs in both cases revealed areas of frosted glass darkening. Since no data was obtained for coronavirus infection (negative tests for coronavirus, lack of antibodies), changes in the lungs were interpreted as a consequence of constant aspiration of CSF. The patients were admitted to a separate ward. Both patients underwent endoscopic endonasal plasty of the skull base defect. The postoperative period in both cases was uneventful. In both cases, the patients underwent computer tomography scan of the chest organs one month later. On the photographs, the signs of pneumonia completely regressed.

[Nosocomial meningitis in endoscopic transsphenoidal surgery]. / Nozokomial'nye meningity v endoskopicheskoi transsfenoidal'noi khirurgii.

One of the main problems of transsphenoidal surgery is the risk of infectious complications. Nosocomial meningitis (NCM) can lead to increased length of hospital stay and financial costs, poor treatment outcomes and even mortality. This complication is an indicator of the quality of medical care for patients with neurosurgical diseases. The purpose of the review was to study the main risk factors of NCM, modern schemes for antibiotic prophylaxis and treatment of this complication after endoscopic transsphenoidal surgery. The main risk factors of meningitis are intra- and postoperative CSF leakage, overweight, diabetes mellitus, previous transsphenoidal surgeries and radiotherapy. To date, there are no generally accepted periods for antibiotic prophylaxis in nasal CSF leakage, installed external ventricular / lumbar drains or tampons in nasal cavity. Antibiotic prophylaxis should not exceed 3 postoperative days due to the risk of cultivating the drug-resistant organisms. If NCM is detected, treatment should be initiated immediately with a broad spectrum of antibiotics.

[Risk factors of nosocomial meningitis in neurological intensive care unit. Results of a five-year prospective study]. / Faktory riska razvitiya nozokomial'nykh meningitov u patsientov neirokhirurgicheskogo profilya v otdelenii reanimatsii i intensivnoi terapii. Rezul'taty pyatiletnego prospektivnogo issledovaniya.

Nosocomial meningitis (NM) is a serious complication in neurosurgery. Understanding the risk factors of nosocomial meningitis is important for their prevention. OBJECTIVE: To determine the main risk factors of NM in neurological intensive care unit. MATERIAL AND METHODS: A prospective study included all patients (n=2140) treated at the neurological intensive care unit for more than 48 hours between October 1, 2010 and October 31, 2015. Cases of nosocomial meningitis were registered. We analyzed risk factors in 2 groups of patients (with and without NM). RESULTS AND DISCUSSION: The incidence of NM in neurological intensive care unit was 8.4% (95% CI 6.8-10.0) (n=180). Relative risk of NM under external ventricular drainage was 3.98 (99 cases of NM, p<0.05). Relative risk of NM in patients with CSF leakage (including nasal CSF leakage after transsphenoidal surgery) was 5.2 (49 cases of NM, p<0.05). The incidence of nosocomial meningitis was significantly higher among patients with surgery time ≥8 hours (17.68%, p<0.01). Nosocomial meningitis was also significantly more common after redo surgery (13.07%, p<0.05). Insertion of intracranial pressure sensor was not a significant risk factor of NM. The risk of meningitis was 2.67% if the above-mentioned factors were absent. Extracranial factors are not specific for NM. No significant relationship between certain neurosurgical disease and NM was found. CONCLUSION: We found higher risk of NM in ICU patients with the following factors: external ventricular drainage, CSF leakage, redo surgery and surgery time.

The sensitivity of planktonic cultures and biofilms of gram-negative bacteria to commercial disinfectant and antiseptic preparations.

The in vitro antibacterial activity of 11 commercial disinfectant preparations and 8 antiseptics against 10 strains of the bacteria Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloaceae and Providencia stuartii obtained from international collections and isolated from neuroresuscitation patients in Moscow in 2018 was studied. The sensitivity of planktonic cultures to the preparations was determined by the method of serial dilutions in broth and the spot method on solid nutrient media, the sensitivity of biofilms by the applicator method. A general pattern was revealed: the level of sensitivity to tested disinfectants in clinical strains was lower than in reference strains. It was found that the disinfectants «Mikrobak-Forte¼, «SAT-22¼, «Neobak-Oksi¼ at the concentrations recommended by the manufacturers were effective against bacteria of all test strains, both in the plankton state and in the form of biofilms. On the contrary, the disinfectant preparations «Biodez-Optima¼, «Biodez-Extra DVU¼, «Novodez-Aktiv¼, «Triosept-Oksi¼, «Tristel Fusion for Surfaces¼, «Effect-Forte Plus¼, «Lactic-Oxy¼ did not have sufficient effectiveness in the concentrations recommended by the manufacturers, therefore it is proposed to use these drugs in higher concentrations. It was found that the disinfectant «Biodez-Extra DVU¼ is able to inhibit the growth of biofilms of bacteria of the species K. pneumoniae. The ability to suppress the growth of bacterial biofilms of K. pneumoniae, A. baumannii, P. aeruginosa was revealed for the «Triestel Fusion for surfaces disinfectant¼. The bacteria of all used test strains in the planktonic state were sensitive to all tested antiseptic preparations. However, the biofilms of the clinical strains of P. aeruginosa and P. stuartii. possessed resistance to the antiseptics «Octenidol¼, «Octenisept¼, «Miramistin¼, «Hexoral¼. Our studies indicate the need for sensitivity analysis of antibacterial drugs in representatives of hospital pathogens, including the modeling of bacterial biofilms, which is a very relevant and important scientific direction, necessary to improve the control of nosocomial infections in the Russian Federation.

[Randomized study of tolerability, safety and efficacy of Pletax in intermittent claudication]. / Randomizirovannoe issledovanie perenosimosti, bezopasnosti i éffektivnosti preparata Pletaks pri peremezhaiushcheisia khromote.

AIM: This study was aimed at assessing tolerability, safety and therapeutic efficacy of Pletax® (cilostazol) compared with Trental® (pentoxifylline) in patients with moderate-to-severe intermittent claudication. PATIENTS AND METHODS: The study included a total of one hundred 40-to-65-year-old patients presenting with confirmed diagnosis of moderate-to-severe intermittent claudication. Depending on the therapeutic regimen, the patients were divided into two groups. Group 1: 50 patients orally took Pletax® (cilostazol) at a dose of 100 mg twice daily 30 minutes before meals or 2 hours after meals together with conventional therapy. Group 2: 50 patients took oral Trental® (pentoxifylline) in a dose of 400 mg 3 times daily 30 minutes before meals or 2 hours after meals along with conventional therapy. The duration of the follow up period amounted to 24 weeks for both groups. The treadmill test was carried out at room temperature, with the running track tilt angle of 0° at a speed of 3 km/h. The primary parameters of efficacy were as follows: the dynamics of the minimal walking distance (a distance walked by the patient until the appearance of pain in the extremity) and dynamics of the maximal walking distance (a distance walked by the patients until full stop due to pain in the extremity). RESULTS: Analysing efficacy demonstrated higher results of Pletax® compared with Trental®. The obtained findings suggested that Pletax® showed a significant clinical effect as soon as at 2 weeks, followed by advantage during the whole period of follow up. Analysing the parameters of the minimal and maximal walking distances in the group of patients taking Pletax® demonstrated clear superiority over the Trental® group as soon as by week 2 of administration, which preserved during the whole follow-up period. The minimal pain-free walking distance in the Pletax group at baseline amounted to 92.9±83.4 m (Trental group - 92.3±78.4; p=0.3), followed by an increase at week 8 to 126±115 m (Trental group - 116±96.3; p=0.51), at week 16 to 136±116 m (Trental group - 118±95.5; p=0.04), at week 24 to 149±126 b (Trental group - 127±98.9; p=0.01). At the same time, the effect of Pletax® and Trental® on the secondary parameter of efficacy, i.e., the ankle-brachial index was comparable: at baseline - 0.472 and 0.482 (p=0.28), at 2 weeks - 0.48 and 0.483 (p=031), at 8 weeks - 0.49 and 0.485 (p=0.74), at 16 weeks - 0.494 and 0.492 (p=0.2), at 24 weeks - 0.501 and 0.496 (p=0.45). CONCLUSION: The obtained findings demonstrated advantages of Pletax® over Trental®, manifesting themselves in the achievement of the highest parameters by such criteria as the minimal and maximal walking distance. High safety and efficacy of Pletax® were confirmed by low frequency of unfavourable events during therapy.

Recombinant ß-Glucocerebrosidase specific immunoaffinity ligands selected from phage-displayed combinatorial scFv libraries.

Antibodies specific to ß-Glucocerebrosidase were selected from phage displayed naïve scFv libraries. Biopannings were performed against recombinant human protein ß-Glucocerebrosidase immobilized on polystyrene surface, specific phages were eluted with 50% ethylene glycol in citrate buffer (pH 6.0). Several specific binders were discovered and converted to full-size hIgG1 antibodies leading to highly stable binders with dissociation constants (Kd) in the range 10-40 nM. The antibodies were used further as ligands for affinity chromatography, where efficient and selective recovery of biologically active ß-Glucocerebrosidase from cultured media of Chinese hamster ovary cells was demonstrated. ß-Glucocerebrosidase was purified to nearly homogeneous state and had specific activity comparable to the commercially available preparations (40-44 U/mg protein). The obtained immunoaffinity sorbents have high capacity and can be easily regenerated.

[The association of GSTP1 polymorphisms with male idiopathic infertility].

AIM: To identify the association between Ile105Val, Ala114Val polymorphisms of gene GSTP1 (glutathione transferase pi1) and infertility in Russian men. MATERIALS AND METHODS: A total of 160 infertile Russian men of reproductive age (mean age 30.2+/-3.6 years) were included in study group, while in control group there were 104 age-matched healthy fertile Russian male (mean age 31.3+/-5.4 years). Molecular and genetic studies of Ile105Val, Ala114Val polymorphisms of gene GSTP1 were performed using real-time polymerase chain reaction. Genomic DNA was extracted from the peripheral blood. RESULTS: A frequency of genotypes (p=0.024; df=2; p=0.024) and alleles (z=2,778; p=0,005) of Ile105Val locus was significantly different in the study and control group. In the study group, there was an increase in the frequency of the Ile/Ile genotype by 13% (=3.995; df=1; p=0.046) and a decrease in the frequency of the Val/Val genotype by 6% (=4.887; df=1; p=0.027). A rate of genotype Ile/Ile in infertile men with was 1.7 time higher than in control group (odds ratio (OR):1.73; 95% confidence interval (Cl): 1.04-2.87; p<0.05). There was not significant difference in frequency of genotypes and alleles of Ala114Val polymorphism of gene GSTP1 between the study and control groups. CONCLUSIONS: The male infertility in Russia is associated with Ile105Val polymorphism and not associated with Ala114Val polymorphism of gene GSTP1. In infertile men wild-type genotype and major allele Ile105Val polymorphism of gene GSTP1 were significant more frequent compared to control group. A rate of genotype Ile/Ile in men with infertility was 1.7 time higher.

[Monitoring of adverse event triggers as a tool for managing the medical care quality at a neurosurgical clinic. Invitation to the discussion]. / Monitoring triggerov neblagopriiatnykh sobytii kak instrument upravleniia kachestvom meditsinskoi pomoshchi v neirokhirurgicheskoi klinike. Priglashenie k diskussii.

Management of the healthcare quality and safety is one of the priorities of state policy for protecting health of Russian citizens. We describe modern technologies for managing the quality of medical care and patient safety based on a systematic approach. Potential applications of these technologies in neurosurgical practice are defined. Quantitative, qualitative, and basic indicators are proposed for evaluation of outcomes (results) as part of implementation of an integrated quality management system in neurosurgical practice.

[Influence of distal misalignment of the mandible on the development of postural pathology]. / Vliianie distal'nogo smeshcheniia nizhnei cheliusti na razvitie postural'noi patologii.

The aim of this study was to study the relationship between the distal displacement of the mandible in the temporomandibular joint (TMJ) with postural pathology. We examined 20 people from the control group (age 18-25 years) and 70 patients of the same age with temporomandibular joint dysfunction (TMJD) complicated by dentoalveolar anomalies (distal bite - 27 persons, orthognathic with anomalies of the position of individual teeth - 18, deep - 16, mesial - 4, straight - 2, open - 2, cross - 1), before and after treatment with occlusive tires. Cone beam computer tomography (CBCT) of the TMJ and photometric analysis were made to all those examined. The CBCT analysis was carried out according to the method developed by us, photometric analysis - with the help of the computer program developed by us. Thus, as a result of the study in patients with TMJD complicated by dentoalveolar anomalies were detected significant displacement of the mandible backwards and upwards, as well as according to the photometric analysis of the presence of postural disorders both in the frontal plane (the change of the head position relative to the shoulders and horizontally, impaired facial configuration in the form of an asymmetry of the arrangement of the lines of the eyes, the corners of the mouth and shoulders) and in the sagittal (the forward displacement of the head and the inclination of the vertical axis of the body forward). Treatment of patients with occlusive tires allowed to normalize the position of the lower jaw and posture.

Strong Neutron Pairing in core+4n Nuclei.

The emission of neutron pairs from the neutron-rich N=12 isotones ^{18}C and ^{20}O has been studied by high-energy nucleon knockout from ^{19}N and ^{21}O secondary beams, populating unbound states of the two isotones up to 15 MeV above their two-neutron emission thresholds. The analysis of triple fragment-n-n correlations shows that the decay ^{19}N(-1p)^{18}C^{*}→^{16}C+n+n is clearly dominated by direct pair emission. The two-neutron correlation strength, the largest ever observed, suggests the predominance of a ^{14}C core surrounded by four valence neutrons arranged in strongly correlated pairs. On the other hand, a significant competition of a sequential branch is found in the decay ^{21}O(-1n)^{20}O^{*}→^{18}O+n+n, attributed to its formation through the knockout of a deeply bound neutron that breaks the ^{16}O core and reduces the number of pairs.

Quasifree (p, 2p) Reactions on Oxygen Isotopes: Observation of Isospin Independence of the Reduced Single-Particle Strength.

Quasifree one-proton knockout reactions have been employed in inverse kinematics for a systematic study of the structure of stable and exotic oxygen isotopes at the R^{3}B/LAND setup with incident beam energies in the range of 300-450 MeV/u. The oxygen isotopic chain offers a large variation of separation energies that allows for a quantitative understanding of single-particle strength with changing isospin asymmetry. Quasifree knockout reactions provide a complementary approach to intermediate-energy one-nucleon removal reactions. Inclusive cross sections for quasifree knockout reactions of the type ^{A}O(p,2p)^{A-1}N have been determined and compared to calculations based on the eikonal reaction theory. The reduction factors for the single-particle strength with respect to the independent-particle model were obtained and compared to state-of-the-art ab initio predictions. The results do not show any significant dependence on proton-neutron asymmetry.

[Intra-optic nerve and chiasmal abscess caused by methicillin-resistant Staphylococcus aureus (a case report and literature review)]. / Abstsess intrakranial'noi chasti zritel'nogo nerva i khiazmy, vyzvannyi metitsillinorezistentnym zolotistym stafilokokkom (klinicheskoe nabliudenie i obzor literatury).

A 27-year-old immunocompetent male with headache, transient polydipsia, and polyuria suddenly developed visual impairment (predominantly in the left eye) and, 2 days later, left-sided amaurosis. MRI in T1, T2, DWI, and FLAIR modes revealed a space-occupying lesion of the left intracranial optic nerve and chiasm. According to the clinical X-ray picture, malignant chiasmal glioma was suspected; another and less likely variant was lymphoma. An open biopsy of the space-occupying lesion of the chiasmal-sellar region revealed purulent-necrotic masses. Material from the operative wound was positive for a Staphylococcus aureus strain. The polymerase chain reaction of a cerebrospinal fluid sample revealed methicillin-resistant Staphylococcus aureus. The patient underwent systemic and intrathecal antibiotic therapy with linezolid and vancomycin, respectively, with a good clinical effect: there was an improvement in the vision in a right single sighted eye and normalization of the cerebrospinal fluid composition.

Role of Glutathione-S-Transferase Family Genes in Male Infertility.

Polymorphisms of xenobiotic detoxification genes GSTT1 and GSTM1 and activity of glutathione system enzymes were studied in men with infertility. The frequency of deletion variant of GSTT1 gene in men with infertility was by 2 times higher than in fertile men. Deletion variant of GSTM1 gene was 1.4-fold more frequent in infertile men than in fertile men. Complete deletion of two genes was found in 19% men with infertility and only in 6% fertile men. The balance of activity of glutathione system enzymes essential for the effective detoxification of exogenous xenobiotics and toxic endogenous metabolites was impaired in infertile carriers of deletion variants of genes. Our results suggest that adaptation mechanisms are disordered in infertile men.

3111T/C Clock Gene Polymorphism in Women with Insomnia.

Comparative analysis of the frequency distributions of genotypes and alleles of 3111T/C Clock gene polymorphism was carried out in climacteric Caucasian women with and without insomnia. Genotype TT is more incident in women with insomnia (55.5% vs. 42.6% in the control). Allele T predominated in the control and study group and its frequency is higher in women with insomnia. The OR for the risk of insomnia realization is 1.78 (95%CI 1.16-2.75). No association between genotypes and complaints of patients with insomnia is detected.

Features of Lipoperoxidation, Antioxidant Defense, and Thiol/Disulfide System in the Pathogenesis of Infertility in Males, Carriers of Nonfunctional Variants of GSTT1 and GSTM1 Gene Polymorphisms.

Comparative analysis of the parameters of LPO, antioxidant defense (AOD), and the thiol/disulfide system was performed in fertile and infertile males of reproductive age carrying different genotypes of the glutathione system genes. Blood plasma, blood hemolysate, and ejaculate served as specimens for biochemical studies. A decrease in glutathione S-transferase activity was found in blood and ejaculate specimens from fertile and infertile carriers of nonfunctional GSTT1(0/0)/GSTM1(0/0) genotypes. In infertile carriers of nonfunctional GSTT1(0/0)/GSTM1(0/0) genotypes determining reduced glutathione S-transferase activity, a decrease in the concentration of low-molecular-weight cell antioxidant (reduced glutathione) and an increase in the concentration of secondary LPO products (TBA-reactive substances) were revealed. Identification of carriers the polymorphic GSTT1 and GSTM1 variants and analysis of activity of the thiol/disulfide system enzymes can be recommended for additional evaluation of the risk for reproductive dysfunction in men.

[Association of polymorphism of GSTT1 and GSTM1 genes with infertility in men].

AIM: To identify the association between homozygous deletion genotypes of glutathione transferase genes GSTT1 (glutathione transferase theta 1), GSTM1 (glutathione S-transferase mu1) and infertility in Russian men. MATERIALS AND METHODS: The article presents a comparative analysis of the incidence of homozygous deletion genotypes of glutathione transferase genes GSTM1 and GSTT1 in Russian men with and without infertility. The study group comprised 160 infertile Russian men of reproductive age (mean age 30.2+/-3.6 years.) The infertility diagnosis was verified according to the WHO guidelines. The control group comprised 104 healthy Russian volunteers (mean age 31.3+/-5.4 years.) Molecular genetic detection of GSTM1 and GSTT1 deletion polymorphisms was performed using PCR. The genomic DNA for the study was extracted from whole blood samples. RESULTS: The study and control group differed significantly in incidence of GSTM1 (p=0.043) and GSTT1 (p=0.008) deletion polymorphisms. The probability of detecting "zero" genotypes of the GSTT1 and GSTM1 genes in infertile men was 2.5 (p<0.05) and 1.7 times higher (p<0.05), respectively, than in fertile men. CONCLUSIONS: Therefore, the study findings allow us to conclude that the deletion genotypes of GSTM1 and GSTT1 are associated with infertility in Russian men. Molecular genetic analysis of deletion polymorphism of glutathione transferase genes can be recommended for a comprehensive examination of infertile men.

[Drainage-associated meningitis in neurocritical care patients. The results of a five-year prospective study]. / Drenazh-assotsiirovannye meningity u patsientov otdeleniia neiroreanimatsii. Rezul'taty piatiletnego prospektivnogo nabliudeniia.

AIM: to determine the incidence rate and risk factors for drainage-associated meningitis in neurocritical care patients. MATERIAL AND METHODS: The prospective study included 539 patients who spent more than 48 h at the Department of Neurocritical Care and underwent external ventricular drainage. The incidence rate and risk factors for drainage-associated meningitis were evaluated. RESULTS: Over a 5-year period, 2140 patients have been hospitalized to the Department of Critical and Intensive Care (DCIC) for more than 48 h; of these, 539 patients underwent external ventricular drainage (EVD). Drainage-associated meningitis developed in 99 patients, which amounted to 19.8 (CI 16.3-23.3) per 100 patients with drainage and 18.3 (CI 14.3-22.2) per 1000 days of drainage. The incidence rate of drainage-associated meningitis did not significantly correlate with different neurosurgical diseases, but there was a tendency for meningitis to predominate in EVD patients with vascular pathology of the central nervous system (CNS). The rate of artery catheterization for direct measurement of systemic BP and the use of vasopressor agents were significantly higher in the group of patients with drainage-associated meningitis (p<0.05). ALV was used in 98 (99%) of 99 patients with drainage-associated meningitis; respiratory support was used in 325 (80.8%) patients without meningitis (p<0.01). An analysis of the ventricular drainage duration revealed a significantly (p<0.05) larger number of days of using EVD in the group of patients with drainage-associated meningitis. In most critical care patients (57.6%), meningitis developed during the first week of drainage. Cerebrospinal fluid leakage occurred significantly more frequently in patients with drainage-associated meningitis than in patients with EVD and without meningitis (p<0.01). Based on a microbiological examination, the etiology of drainage-associated meningitis was established in 57.1% of cases. The leading pathogens were coagulase-negative staphylococci (48.3%) and Acinetobacter baumannii (18.3%). CONCLUSION: The incidence rate of drainage-associated meningitis was 19.8 per 100 patients and 18.3 per 1000 days of drainage. The risk factors significantly predominating in patients with drainage-associated meningitis include the duration of drainage, association with external CSF leakage, as well as factors associated with indicators of the overall severity of the condition.

Oxidative Stress and Catalase Gene.

We studied the frequency of alleles and genotypes of CAT gene -262C>T polymorphism (rs1001179) in Russian and Buryat adolescents. The frequency of -262T allele was 28.31% in Russians and 16.84% in Buryats (p<0.01). In both ethnic groups, a correlation between the study polymorphism and concentration of diene conjugates was observed. Carriers of TT-genotype of CAT gene-262C>T polymorphism had lower level of diene conjugates than carriers of CT- and CC-genotypes.

Phagebiotics in treatment and prophylaxis of healthcare-associated infections.

We have developed a phagebiotic composition using 8 virulent bacteriophages (2 strains of each species) which are able to lyse Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. The unique character of the developed composition is ensured by particular properties of each bacteriophage comprising the preparation, including their range of lytic activity toward specific bacterial pathogens, morphology of their plaques, cycle of their development, restriction profile of their DNAs, specificity of their genomes (based on complete genome sequencing), and other properties. The preparation did not produce any signs of acute or chronic intoxication in the experimental animals. Therapeutic and prophylactic efficiency of the phagebiotic composition was demonstrated in the prevention and treatment of the experimental acute K. pneumoniae infection in mice. The investigations have shown that the preparation possesses a high therapeutic efficiency and is highly competitive with ciprofloxacin which is very effective against the infective strain K. pneumoniae. Our small-scale clinical trial was aimed to evaluate therapeutic effectiveness of the phagebiotic composition in an epidemiological emergency situation in an intensive care unit, caused by multi-resistant strains of Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Seventy nine per cent of the initial samples from 14 patients' endotracheal aspirate, blood and urine were contaminated. Twenty-four hours after the 3-day phage therapy (20 ml of cocktail at a titer for each phage 108 pfu/ml were introduced intragastrically through a tube once a day) contamination level dropped to 21%. Hence the obtained results enabled us to create a new phagebiotic composition that may be used as an alternative to antibiotics to treat these healthcare-associated infections.