[Potential complications of patient positioning in spine surgery]. / Vozmozhnye oslozhneniya pozitsionirovaniya neirokhirurgicheskikh patsientov pri operatsiyakh na pozvonochnike.

Patient position on the operating table during spine surgery is important for optimal intraoperative manipulations. However, this position is far from physiological one. An unnatural position, surgery time and sometimes necessary intraoperative change in body position can lead to certain neurological and somatic complications. Most of these events can significantly reduce the patient's working capacity and quality of life and even result disability. Medical staff placing the patient on operating table, neurosurgeons and anesthesiologists should be aware of risk factors of similar complications and their prevention. The authors describe the most serious and difficult for correction conditions, such as peripheral neuropathy, damage to visual analyzer, as well as optimal method of patient positioning.

Factors of Progression and Occurrence of Atherosclerosis in Rheumatoid Arthritis.

Aim      To determine in a prospective study factors of progressive atherosclerotic lesion of blood vessels in patients with rheumatoid arthritis (RA).Material and methods  This prospective study included 124 patients with RA and suspected ischemic heart disease (IHD) and 30 patients with IHD (comparison group) aged 58 [52; 63] years. On enrollment to the study and at 3 years of follow-up, all patients underwent clinical and instrumental examination according to European and Russian guidelines for diagnosis and treatment of stable IHD (2013), including coronography as indicated. For all RA patients of the comparison group, risk factors (RF) were evaluated, including arterial hypertension, smoking, excessive body weight, family history of cardiovascular diseases (CVD), diabetes mellitus, and dyslipidemia. The following laboratory data were evaluated: blood count; biochemistry, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), rheumatoid factor (RhF), cyclic citrullinated peptide antibodies, and high-sensitivity C-reactive protein (hsCRP). Proinflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF- α), were measured in RA patients once, at 3 years of follow-up.Results Incidence of FRs for CVD was similar in RA patients and in the comparison group. Median RA duration before inclusion into the study was 11 years, and median DAS28 index score was 3.8. Incidence of dyslipidemia due to increased TC, LDL-C, and HDL-C was higher for RA patients at baseline. The LDL-C goal (<1.8 mmol/l) was achieved only in 3 (10 %) patients of the comparison group and 10 (8 %) RA patients. RA patients had higher levels of the inflammation indexes, hsCRP (0.75 mg/dl vs. 0.16 mg/dl; p<0.05) and erythrocyte sedimentation rate (ESR) (15 mm/h vs. 11.5 mm/h; p<0.05). In the RA group at baseline, atherosclerotic plaques with carotid artery (CTA) stenosis of 20% or more were found in 94 (77 %) patients; in 3 of them, CA stenosis was >50%. Patients with RA frequently had unchanged or slightly changed coronary arteries (CA) (47% of patients), and less frequently they had hemodynamically significant multi-arterial coronary atherosclerotic lesions (7 % vs. 57 % of patients in comparison group). At 37.5 months, 21 (23 %) of 94 RA patients had progressive atherosclerosis in CA and/or CTA; 12 (13 %) RA patients had only progressive CA atherosclerosis; 7 (8 %) had only progressive CTA atherosclerosis; and 2 (2 %) had simultaneous progression of CA and CTA atherosclerosis. Two groups of RA patients were formed, with the progression of atherosclerosis (n=21) and without the progression of atherosclerosis (n=69). RFs for the development/progression of atherosclerosis in RA patients included smoking, family history of CVD, and duration of the disease. Levels of lipids did not differ. Levels of proinflammatory cytokines (IL-1ß, IL-6, TNF-α) were higher in RA patients with progressive atherosclerosis. No effects of the anti-rheumatic therapy on the progression of atherosclerosis were observed.Conclusion      Progression of atherosclerosis in RA remains in disease with low and moderate activity during the anti-rheumatic and hypolipidemic treatment. The development of atherosclerosis in RA is determined by lipid, inflammatory, and immune disorders.

[Application of cardiovascular risk scales to identify carotid atherosclerosis in patients with rheumatoid arthritis].

AIM: To evaluate the cardiovascular risk (CVR) and analyze its relationship with detection of early carotid artery atherosclerotic lesion in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: One hundred and nine RA patients aged 45 to 60 without established cardiovascular diseases (CVD) were included in the study. The median age was 52 [48; 54] years, duration of RA was 120 [36; 204] months, DAS28 was 4.7 [3.5; 5.6] points. CVD risk was calculated with mSCORE, Reynolds Risk Score (RRS), ASSIGN, QRISK3, ERS-RA scales and Carotid Artery Doppler Ultrasound Exam was performed for all patients. RESULTS: High risk was found in 5, 5, 14, 6, and 38% of patients according to mSCORE, RRS, ASSIGN, QRISK3, ERS-RA scales, respectively. Atherosclerotic plaques of carotid arteries were found in 30% of patients. It was found that carotid intima-media thickness is correlated to all CVR calculators, age, systolic and diastolic blood pressure, cholesterol, erythrocyte sedimentation rate, interleukin-6 levels. The sensitivity and specificity of the CVR algorithms in prognostication of atherosclerotic carotid artery lesions were 73 and 67% for mSCORE, 64 and 63% for RRS, 64 and 56% for ASSIGN, 73 and 49% for QRISK3, respectively, p0.05 in all cases, 67 and 50% for ERS-RA, p=0.06. CONCLUSION: RRS, mSCORE, ASSIGN, QRISK3 calculators equally predict atherosclerotic carotid artery damage in RA patients. The optimal ratio of specificity and sensitivity is shown for the mSCORE scale. Stratification of CVR in RA patients should include assessment of the carotid intima-media thickness. To identify CVR in RA patients, the most informative methods are mSCORE calculation and carotid intima-media thickness determination.

Synthesis and biological evaluation of 6-nitro-1,2,4-triazoloazines containing polyphenol fragments possessing antioxidant and antiviral activity.

Stable σ-adducts of azolo[5,1-c]triazines and azolo[1,5-a]pyrimidines with different polyphenols were synthesized and their antioxidant and antiviral activity were investigated. Their affinity to viral hemagglutinin was assessed using molecular modelling. The phloroglucinol-modified azolo-azines possessed the highest virus-inhibiting activity. According to the results of the study of antioxidant properties of compounds, the most promising ones exhibiting highest antioxidant capacity were adducts containing in their structure pyrogallol and catechol residues and 6-nitro-triazolotriazin-7-ol scaffold. No correlation between antioxidant and virus-inhibiting activity of compounds studied was detected. The most active compounds demonstrated the ability to prevent binding of viral hemagglutinin with cellular receptor as shown in hemagglutination inhibition assay. Our results demonstrate that polyphenol-modified azolo-azines are prospective for further optimization as potential antivirals and that their action is directed against viral hemagglutinin.

An integrated approach to the investigation of antioxidant properties by potentiometry.

An analytical methodology is proposed for a comprehensive study of antioxidant properties of various objects based on the implementation of various mechanisms of antioxidant action. In order to interpret results regarding the action of antioxidants in living organisms it is proposed to adhere to certain requirements for research methods of antioxidant properties, for oxidizing agents of a radical and non-radical nature. The developed integrated approach consists in using the potentiometry method and is based on the antioxidant capacity determination which is founded on the interaction of antioxidants with the К3[Fe(CN)6] by the ET-mechanism and the conjugation mechanism and the antiradical capacity determination based on the interaction of antioxidants with peroxyl radicals by the HAT-mechanism. Individual antioxidants of natural origin, plant materials extracts as well as synthesized 6-nitro-1,2,4-triazoloazin containing polyphenols fragments, which are complex conjugated structures, have been investigated. It has been shown that in the antioxidants study it is advisable to use the integrated approach that will allow to evaluate antioxidant properties from the point of view of various antioxidants action mechanisms.

[Level of N-terminal fragment of brain natriuretic peptide progenitor and atherosclerotic damage of brachocephalic arteries in patients with rheumatoid arthritis with inefficiency and/or injurability of basic anti - inflammatory treatment].

The high prognostic significance of the concentration of the N-terminal - pro-B-type natriuretic peptide (NT-proBNP) in the development of cardiovascular diseases (CVD) was identified for rheumatoid arthritis (RA) and general populations. AIM: to investigate the significance of NT-proBNP level in patients (pts) with RA with the ineffectiveness and/or intolerance of basic anti - inflammatory therapy; compare the level of NT-proBNP with atherosclerotic lesion of the brachiocephalic arteries (BCA), traditional risk factors and inflammatory markers. MATERIALS AND METHODS: The investigation enrolled 28 pts (24women/4men) with the lack of efficacy/resistance and/or intolerance of basic anti - inflammatory drugs (DMARDs); median age was 55 [46; 61] years, median disease duration 114 [60; 168] month; DAS28 6,2 [5.1; 7.0]; SDAI 35.0[23.9; 51.0], CDAI 30.0[21.0; 42.0], serum positivity for rheumatoid factor (RF) (100%)/anti - cyclic citrullinated peptide antibodies (ACCP) (86%). The study did not include RA pts with congestive heart failure. High incidence of traditional risk factors was found in RA pts: arterial hypertension - in 75%, dyslipidemia - 61%, smoking - 17%, overweight - 61%, family history of cardiovascular diseases - 36%, hypodynamia - 68%. Coronary artery disease was diagnosed in 11% RA pts. Lack of efficacy of 3 or more DMARDs was found in 46% of pts, intolerance to previous therapy with DMARDs - in 54% pts. 47% were receiving methotrexate (20 [18; 25] mg/week), 11% - leflunomide, 7% - sulfasalazine, 46% - glucocorticoids, 75% - non - steroidal anti - inflammatory drugs. The control group consisted of 20 healthy donors, comparable to pts by age and sex. Serum levels of of NT-proBNP were measured using electrochemiluminescence method Elecsys proBNP II (Roche Diagnostics, Switzerland). The determination of the intima - media thickness (IMT) BCA were assessed from duplex scanning. Atherosclerotic lesion of BCA was assessed by the presence of atherosclerotic plaque (IMT ≥1.2 mm). RESULTS: NT-proBNP concentrations in RA pts proved to be higher (78.7 [41.4; 101.3] pg/ml) than those in the control group (55.3 [36.6; 67.3] pg/ml, p100 pg/ml - 1 group (n=6) and ≤100 pg/ml - 2 group (n=22). Groups of RA pts did not differ in gender, age, activity of RA, frequency of detection of traditional risk factors. Atherosclerotic lesion of the BCA was detected in 3 (50%) pts of the 1 group and in 8 (36%) pts of the 2 group (p>0.05). In RA pts the level of NT-proBNP correlated with age (r=0.39; p.

Polyprenyl Phosphates Induce a High Humoral and Cellular Response to Immunization with Recombinant Proteins of the Replicative Complex of the Hepatitis C Virus.

The search for new adjuvants remains the critical task for the creation of hepatitis C vaccines due to the weak immunogenicity of biotechnological products. When immunizing mice with the recombinant proteins NS3 and NS5B of the hepatitis C virus (HCV), the adjuvant activity of three immunomodulators was compared. Phosprenyl® on the basis of polyprenyl phosphate (PPP), chemically synthesized analogue of the bacterial cell wall glucosaminyl muramyl dipeptide (GMDP), and IFN-α recombinant protein were tested. GMDP increased the activity of IgG1 antibodies 4-6 times but did not stimulate the production of IFN-γ; IFN-α has not shown any adjuvant properties. The introduction of recombinant HCV proteins together with PPP in low doses increased the activity of IgG2a isotype antibodies 4-7 times and increased IFN-γ secretion 3 times. Thus, it was first shown that PPP polarizes the immune response to Th1-type and is a promising adjuvant for the development of a vaccine against hepatitis C.

Mechanisms of hydrogen sulfide (H2S) action on synaptic transmission at the mouse neuromuscular junction.

Hydrogen sulfide (H2S) is a widespread gasotransmitter also known as a powerful neuroprotective agent in the central nervous system. However, the action of H2S in peripheral synapses is much less studied. In the current project we studied the modulatory effects of the H2S donor sodium hydrosulfide (NaHS) on synaptic transmission in the mouse neuromuscular junction using microelectrode technique. Using focal recordings of presynaptic response and evoked transmitter release we have shown that NaHS (300 µM) increased evoked end-plate currents (EPCs) without changes of presynaptic waveforms which indicated the absence of NaHS effects on sodium and potassium currents of motor nerve endings. Using intracellular recordings it was shown that NaHS increased the frequency of miniature end-plate potentials (MEPPs) without changing their amplitudes indicating a pure presynaptic effect. Furthermore, NaHS increased the amplitude of end-plate potentials (EPPs) without influencing the resting membrane potential of muscle fibers. L-cysteine, a substrate of H2S synthesis induced, similar to NaHS, an increase of EPC amplitudes whereas inhibitors of H2S synthesis (ß-cyano-L-alanine and aminooxyacetic acid) had the opposite effect. Inhibition of adenylate cyclase using MDL 12,330A hydrochloride (MDL 12,330A) or elevation of cAMP level with 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (pCPT-cAMP) completely prevented the facilitatory action of NaHS indicating involvement of the cAMP signaling cascade. The facilitatory effect of NaHS was significantly diminished when intracellular calcium (Ca(2+)) was buffered by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester (BAPTA-AM) and ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid acetoxymethyl ester (EGTA-AM). Activation of ryanodine receptors by caffeine or ryanodine increased acetylcholine release and prevented further action of NaHS on transmitter release, likely due to an occlusion effect. Inhibition of ryanodine receptors by ryanodine or dantrolene also reduced the action of NaHS on EPC amplitudes. Our results indicate that in mammalian neuromuscular synapses endogenously produced H2S increases spontaneously and evoked quantal transmitter release from motor nerve endings without changing the response of nerve endings. The presynaptic effect of H2S appears mediated by intracellular Ca(2+) and cAMP signaling and involves presynaptic ryanodine receptors.

Potentiometric study of antioxidant activity: development and prospects.

The increasing interest in the study of the antioxidant activity of different objects is caused by an unbalance between the formation of reactive oxygen species (ROS) and the performance of the antioxidant system in humans under certain conditions, which leads to oxidative stress and pathological states of the organism. This article presents a brief critical review of the methods that are used to measure integrated antioxidant activity (AOA). It is shown that the most promising methods for measuring AOA are electrochemical ones, particularly potentiometry, as it best fits the nature of the processes causing oxidative stress. The article gives the theoretical rational for requirements that an oxidizer of antioxidants (AO) should meet. The work presents the thermodynamic grounds for the use of an earlier proposed mediator system, kinetics of chemical reactions between AO and the mediator system. In order to confirm reliability and accuracy of the results, numerous correlation studies were conducted, aiming to compare the data obtained with the use the proposed method and independent analytical methods. The article presents the results of the potentiometric study of AOA for a variety of objects, including individual antioxidant → nutritional supplements → food → blood and blood fractions.

[Cardiovascular diseases in patients with rheumatoid arthritis during long-term methotrexate therapy].

AIM: To compare the prevalence of risk factors, clinical and subclinical manifestations of cardiovascular diseases (CVD) and their complications in methotrexate (MT)-treated and untreated patients with rheumatoid arthritis. SUBJECTS AND METHODS: The investigation enrolled 193 patients (168 women and 25 men) less than 60 years of age (mean age 49 [44; 53] years) with RA. The patients were divided into 2 groups: 1) 69 patients who received MT in a dose of 15.1 [10.2; 21] mg/week for at least 12 months (mean disease duration 25 [18; 48] months); 2) 124 patients who did not take MT. The patient groups were matched for age, gender, disease duration, RA activity, and the rate of rheumatoid factor (RF) seropositivity and extraarticular manifestations. RESULTS: Dyslipidemia was significantly less frequently identified in MT-treated patients (35/69 or 51%) than in MT-untreated ones (85/124 or 69%; p = 0.01). The serum from the patients treated with MT exhibited higher high-density lipoprotein cholesterol concentrations ((1.8 [0.9; 2.0] mmol/l) than in those untreated with MT (1.2 [1.0; 1.6] mmol/l; p = 0,047). In Group 1, hypertension (49%) and diabetes mellitus (3%) were slightly rare than in Group 2 (62 and 13%, respectively; p > 0.05). Carotid atherosclerotic plaques were found in 19 and 16% and intima-media thickness (IMT) enlargement was seen in 53 and 56% of the patients in Groups 1 and 2, respectively. Silent myocardial ischemia was diagnosed in every 10 patients; heart disease (exertional angina, myocardial infarction) was in every 5 patients in both groups. Aortocoronary bypass surgery was performed in 2 (3%) patients from those who received MT and had experienced MI and in one (1.6%) patient from the MT-untreated group. CONCLUSION: Long-term MT therapy was associated with the lower rate of dyslipidemia, but it failed to affect the incidence of CVD in patients with RA.

[Biochemical and hemocoagulation criteria for evaluating the risk of nephropathy development in workers with occupational exposure to dust].

The authors present main mechanisms and leading pathogenetic factors underlying occupationally mediated dust nephropathies. The article covers results of analysis concerning biochemical and hemocoagulation criteria to evaluate the risk of nephropathy in workers exposed to high concentrations of industrial dust aerosols.

[Diagnostic features of focal pulmonary tuberculosis in new cases]. / Osobennosti diagnostiki ochagovogo tuberkuleza legkikh u vpervye vyiavlennykh bol'nykh.

The authors examined 120 new cases of focal pulmonary tuberculosis (FPT) during the good epidemic situation years (1982-1986) and 70 patients during the poor epidemic situation years (1995-1999). The latter years were marked by a worse social composition, more frequent contacts with those isolating bacteria, a more severe course with weight loss, prolonged subfebrile temperatures, anemia, an increasing tendency for lung tissue decay and even in large foci, a more frequent bacterial isolation along with progressive immunodeficiency. New diagnostic technologies, such as computed tomography, T-lymphocytic studies at the subpopulational level by using monoclonal narrow-specific antibodies, adaptive response tests that reflect the body's responsiveness, are of value in diagnosing FPT.

[Causes of fatal outcomes in patients with sarcoidosis]. / Prichiny letal'nykh iskhodov u bol'nykh sarkoidozom.

There have been 21 (7.4) fatal cases among 282 patients with diffuse sarcoidosis of the lung and other organs in the past 30 years. The study of the causes of death indicated that 5 patients had progressive sarcoidosis of the lung and intrathoracic lymph nodes with progressive cardiopulmonary failure. Ten other dead persons had generalized generalized sarcoidosis; sarcoidosis of the central nervous system, liver, spleen, and kidney with marked progressive failure of these organs were of the greatest contribution to death. Concomitant diseases, such as pyoinfection, bronchiectasis with pulmonary hemorrhage, essential hypertension, diabetes, and bronchial cancer, are causes of death in 5 more patients with pulmonary sarcoidosis.

[The effect of anthelmintics on the serotonin content of cestodes]. / Effekt nekotorykh antigel'mintikov na soderzhanie serotonina u tsestod.

The effects of some anthelminthic agents, such as praziquantel, fenasal, albendazole, on the levels of the neurotransmitter serotonin in the tissues of Hymenolepis diminuta cestodes and Mesocestoides corti tetrathyridia were examined in vivo and in vitro. The finding showed lower serotonin levels in H.diminuta after praziquantel and albendazole and in M. corti after fenasal. It is suggested that the serotonin neurotransmitter system of helminths is involved in the mechanism of action of these agents.

[Specific features of diagnosis and treatment of patients with pulmonary sarcoidosis and tuberculosis]. / Osobennosti diagnostiki i lecheniia bol'nykh sarkoidozom v sochetanii s tuberkulezom organov dykhaniia.

In the past 30 years, the authors examined and treated 6473 patients with pulmonary sarcoidosis, of them 105 (1.6%) had contacted with the individuals isolating Mycobacterium tuberculosis and 45 (0.7%) had a history of various forms of pulmonary tuberculosis; however, the patients with pulmonary sarcoidosis had neither exacerbations nor relapses. Of the 6473 patients, 41 (0.63%) was diagnosed as having active pulmonary tuberculosis, including 20 with focal pulmonary tuberculosis, 13 with disseminated pulmonary tuberculosis, 4 pulmonary tuberculosis with infiltrative, and other 4 with destructive pulmonary tuberculosis, disseminated and destructive pulmonary tuberculosis occurred in the progressive pulmonary sarcoidosis. The etiopathogenetic treatment of tuberculosis with at least 3-4 drugs (small-dose hormones, antioxidants, immunomodulators) was found to cure the two abnormalities in 95.2% and in 4.8% of cases, the pathological process became chronic when limited disseminated pulmonary tuberculosis was concurrent with disseminated pulmonary sarcoidosis.

[Arterial pressure and concentrations of blood lipids in the populations of Moscow and Leningrad]. / Arterial'noe davlenie i kontsentratsiia lipidov krovi v populiatsiiakh Moskvy i Leningrada.

Epidemiological investigation of two randomized groups of men born in 1916-1935 (3908 men in Moscow, 3907 in Leningrad) has shown that in both populations there is a direct relationship between the arterial pressure (AP) and the level of total cholesterol (CS), triglycerides (TG) and cholesterol lipoproteids of high density (CS-LPHD) in blood plasma. A strong correlation between the level of the systolic arterial pressure (SAP) and age has been established. Age variations of the lipid levels were insignificant. The total CS, TG, SAP levels and the diastolic AP increase with the growth of the relative body weight, while the CS-LPHD level decreases. In the group engaged in manual labour the total CS and TG levels are simultaneously lowered and those of CS-LPHD and SAP elevated. There is a direct relationship between the level of CS-LPHD, AP and alcohol intake. Smoking somewhat lowers the level of CS-LPHD and AP. The direct relationship between AP and the level of CS-LPHD remains after complex analysis including all the factors studied.

[Amino acid and peptide ratio in protein hydrolysates for parenteral feeding]. / O sootnoshenii aminokislot i peptidov v belkovykh gidrolizatakh dlia parenteral'nogo pitaniia.

Using the method of amino acid analysis and routine methods of protein biochemistry, the ratio of amino acids and peptides in acid and enzyme protein hydrolyzates was determined. Depending on the production procedure, the hydrolyzates under study contained various amounts of free amino acids and peptides in which the number of amino acid residues varied from 2 to 7. Additional hydrolysis of these preparations by leucine aminopeptidase led to a decrease in the peptide content and to an increase in the amino acid content. This may have a beneficial effect on the quality of protein hydrolyzates.