Methods for the Synthesis of γ-Acetopropyl Alcohol.

The methods for the synthesis of γ-acetopropyl alcohol (APA) used for the production of vitamin B1, antimalarial drugs, and polymers are analyzed. Promising APS synthesis methods are the hydrogenation-hydration of sylvane, the hydrogenation of furfural, and syntheses based on allyl acetate, sodium acetoacetic ester, and γ-butyrolactone.

Improvements in Methods for Disease Diagnosis and Monitoring.

A review is made of the main scientific studies presented in the section Methods and Means of Diagnosis and Treatment of Various Diseases of the XIVth International Scientific Conference on Physics and Radio Electronics in Medicine and Ecology (PhREME'2020) held in Vladimir City on July 1-3, 2020.

[Telomere length as a biomarker of the risk of cardiovascular complications in patients with coronary heart disease].

AIM: To study the effect of oxidative stress and telomere length in the chromosomes of blood leukocytes in patients with coronary heart disease (CHD) on the development of cardiovascular complications. MATERIALS AND METHODS: In 119 patients with CHD, the level of oxidatively modified low-density lipoproteins (ox-LDL) in blood plasma and the length of telomeres in nuclear blood cells were determined during the examination. After 5 years, a telephone survey of patients (or their relatives) was conducted to obtain data on the presence of cardiovascular complications. Telomere length was determined using quantitative real-time PCR, and the level of ox-LDL was determined by immunochemical method. RESULTS: It was found that reducing the length of telomeres in patients with CHD increases the risk of subsequent development of cardiovascular complications. A strong negative correlation was found between the level of ox-LDL and telomere length in the group of examined CHD patients who had cardiovascular complications after 5 years. CONCLUSION: CHD patients with short telomere length and high levels of ox-LDL have an increased risk of cardiovascular complications during 5 years.

[Indicator Characterizing Carbonyl-Dependent Modification of Erythrocytic Superoxydismutase as a Biochemical Marker of Oxidative Stress in Coronary Heart Disease].

Aim To study the oxidative modification of red blood cell Cu,Zn superoxide dismutase (SOD) in patients with ischemic heart disease (IHD) in vivo and in vitro to substantiate the use of a new oxidative stress marker.Material and methods Red blood cell Cu,Zn SOD was measured by depression of nitrotetrazolium blue reduction by the superoxide anion generated in xanthine oxidase xanthine oxidation. Red blood cell Cu,Zn SOD was measured immunochemically. The biochemical study was performed in the control group (patients with low extremity fracture without known history of cardiovascular diseases and hyperlipidemia) and in groups of patients with acute myocardial infarction, stable angina, and decompensated heart failure. For evaluation of oxidative stress intensity in IHD patients, an empirical SOD oxidative modification coefficient (OMCSOD) was proposed, which is a Cu,Zn SOD activity / Cu,Zn SOD content ratio.Results The red blood cell Cu,Zn SOD activity was significantly decreased in all IHD groups compared to the control group. Furthermore, OMCSOD was also considerably decreased in IHD patients, which warrants the use of this biochemical index as an oxidative stress marker.Conclusion It was shown that the Cu,Zn SOD modification was induced by interaction of the enzyme molecules with a natural dicarbonyl, malonic dialdehyde, and OMCSOD can be used for evaluation of oxidative stress intensity in IHD patients.

Indolicidin analogs with broad-spectrum antimicrobial activity and low hemolytic activity.

To create a broad-spectrum peptide biocide, we synthesized 45 analogs of antimicrobial peptide indolicidin (H-Ile-Leu-Pro-Trp-Lys-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-NH2). Among them the peptides H-Ile-Leu-Pro-(2-Me)Phe-Lys-(2-Me)Phe-Pro-(2-Me)Phe-(2-Me)Phe-Pro-(2-Me)Phe-Arg-Arg-NH2 and HN2-(CH2)10-Ile-Leu-Pro-D-Phe-Lys-D-Phe-Pro-D-Phe-D-Phe-Pro-D-Phe-Arg-Arg-NH2 have the broadest spectrum of antimicrobial activity and the lowest hemolytic activity. They are active against all 11 tested strains of Gram-positive bacteria, Gram-negative bacteria and fungi with MIC50 from 0.9 to 6.1 µg/ml (0.5 to 3.2 µM), being up to 3 times more active than indolicidin, and are at least 1.8 times less hemolytically active than indolicidin (reached the detection limit). These peptides are patented and could be used for further drug development as antimicrobials.

[An analysis of the structural-topographic interaction of the localization of demyelination and optic nerve lesions in patients with multiple sclerosis]. / Analiz strukturno-topograficheskogo vzaimodeistviia lokalizatsii ochagov demielinizatsii i porazheniia zritel'nogo nerva u patsientov s rasseiannym sklerozom.

AIM: To analyze the interaction between the localization of demyelination plaques and damage to the optic nerve in patients with multiple sclerosis (MS). MATERIAL AND METHODS: Fifty-five patients (18 men and 37 women) with a confirmed diagnosis of MS were examined based on magnetic resonance imaging of the brain (MRI) and the conclusion of a neurologist. Four topographic zones of localization of the visual paths were identified: the orbital part of the optic nerve, periventricular white matter, areas of the right and left thalamus, and white matter of the occipital lobe of the big hemispheres. The MRI data were compared with the results of spectral optical coherence tomography (C-OCT) of the same study. RESULTS: The greatest number of demyelination plaques is described in the periventricular white matter of the lateral ventricles, and the smallest number in the white matter of the occipital lobe of the large hemispheres. In patients with optic neuritis (ON), demyelination plaques were also detected in the projection of the orbital part of ON in 18% of cases. A comparison analysis reveals no correlation between the side of optical nerve lesion and the presence of lesions in the projection of the orbital part of ON. The predictive ability of C-OCT of focal changes in the brain in interaction with C-OCT parameters in groups with ON and partial ON atrophy due to MS is not confirmed. CONCLUSION: In all patients with MS, demyelination plaques are detected in the visual analyzer (VA) projection, even with the manifestation of the disease. In the course of MS progression, their total number increases. Localization of focal demyelination processes in MS in the projection VA and the side of the lesion do not have reliably confirmed the interaction with the parameters of the optic disc in accordance with C-OCT. A lesion of the peripheral neuron VA is identified in all patients.

Protective measures of patients with cardiovascular diseases from exposure to heat waves: medicated and non-medicated.

In conditions of climate warming with an increase in heat waves associated with an increase in cardiovascular morbidity and mortality, the particular interest is the effect of cardiovascular drugs on adaptation to high temperatures. The review reflects the results of European and domestic studies on the safety of therapy during long and short heat waves. Recommendations for the correction of therapy during this period are given. Self-control of blood pressure (SCAD) is a mandatory component of the therapy of arterial hypertension during heat waves. With the development of clinically significant hypotension, a reduction in the dose of antihypertensive drugs is necessary. It is recommended to start with a dose reduction and/or withdrawal of diuretics and nitrates. Not recommended the complete abolition of antihypertensive therapy because of the risk of hypertensive crises, characteristic of abnormal heat, as well as due to the increase in blood pressure when the weather changes and the temperature drops. With increasing blood pressure during heat waves, it is recommended to give preference to calcium channel antagonists, angiotensin converting enzyme inhibitors (ACE inhibitors) and selective beta-blockers. It is necessary to inform patients about the additional protective effect of statins in order to increase adherence to therapy. Patients taking diuretics require individual daily monitoring of fluid intake and body weight. An overview of recommendations on sanogenic behavior during heat waves is given. Details are considered rules for the use of air conditioning, methods of diagnosis of dehydration and drinking mode Keywords: heat waves, cardiovascular complications, preventive measures.

Magnetoplasmonic crystal waveguide.

We propose a perspective type of insulator-metal-insulator magnetoplasmonic crystal waveguide, composed of a gold grating placed between two garnet layers. Using an original non-perturbing method for the deposition of the upper magneto-dielectric layer, we fabricate the samples and provide experimental results evidencing the coupling of surface plasmon-polaritons propagating on the opposite Au/garnet interfaces. In contrast to traditional Au/garnet magnetoplasmonic crystals, spectra of the magneto-optical effect measured in transmission through this waveguide demonstrate rather specific features: a high-quality resonance for the long-range surface plasmon-polariton and a broad 60 nm wide resonance for the short-range surface plasmon-polariton. Our findings open new routes towards the development of high-sensitivity robust magnetoplasmonic sensors.

Antimicrobial activity of the indolicidin-derived novel synthetic peptide In-58.

Natural peptides with antimicrobial activity are extremely diverse, and peptide synthesis technologies make it possible to significantly improve their properties for specific tasks. Here, we investigate the biological properties of the natural peptide indolicidin and the indolicidin-derived novel synthetic peptide In-58. In-58 was generated by replacing all tryptophan residues on phenylalanine in D-configuration; the α-amino group in the main chain also was modified by unsaturated fatty acid. Compared with indolicidin, In-58 is more bactericidal, more resistant to proteinase K, and less toxic to mammalian cells. Using molecular physics approaches, we characterized the action of In-58 on bacterial cells at the cellular level. Also, we have found that studied peptides damage bacterial membranes. Using the Escherichia coli luminescent biosensor strain MG1655 (pcolD'::lux), we investigated the action of indolicidin and In-58 at the subcellular level. At subinhibitory concentrations, indolicidin and In-58 induced an SOS response. Our data suggest that indolicidin damages the DNA, but bacterial membrane perturbation is its principal mode of action. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Successful Tigecycline Use in Combined Therapy of Ventilator-Associated Hospital-Acquired Pneumonia: a Clinical Case.

In patients under artificial lung ventilation (ALV) there is often observed development of severe ventilator-associated pneumonia (VAP) due to polyresistant hospital pathogens. It should be noted that in the patient described here with the initial diagnosis of community-acquired pneumonia rapidly subjected to prolonged ALV the previous antibacterial therapy by broad spectrum drugs significantly increased the risk of contamination just by multiresistant nosocomial strains, which hampered the starting therapy of nosocomial pneumonia either when there were not available or sometimes there were available microbial cultures. When the treatment of severe pneumonias caused by multiresistant hospital flora resistant to carbapenems is actual, in the alternative therapy it could be used tigecycline, a tetracycline from the group of glycylcyclines. A case of successful treatment of nosocomial VAP by tigecycline based on the results of the bronchoalveolar lavage (BAL) culture is described. The case is of interest because tigecycline was used as off label.

[The Relationship Between Level of End-Products of Tissue Glycation and Pulse Wave Velocity in Non-diabetic Patients With Cardiovascular Disease].

AIM: of the study was to assess the relationship between advanced glycation end-products measured by skin autofluorescence (AGEs) and pulse wave velocity (PWV) in non-diabetic patients with cardiovascular disease (CVD). MATERIAL AND METHODS: Skin autofluorescence (AGE--reader, DiagnOptic) and PWV in humero-malleolar segment (PWVhm) were measured in 93 non-diabetic CVD patients (mean age 63.5 years): 28 with ischemic heart disease (IHD) and 65 without IHD from the group with moderate/high risk of development of cardiovascular complications. RESULTS: Significant positive association was observed between AGEs and PWVhm (r = 0.31, p = 0.003). This correlation was found only in patients without IHD (r = 0.44, p < 0.0003). Positive association AGEs with of age (r = 0.52, p = 0.006) was observed irrespective of IHD. AGEs was not the significant determinant of PWVhm in multiple regression analysis. CONCLUSION: Relationship between AGEs and PWVhm was found in non-diabetic moderate/high-risk patients. In contrast to age and systolic blood pressure AGEs was not the significant determinant of PWVhm.

[The Effectiveness of Russian Public Health Recommendations for Sanogennykh Behavior in the Heatwave].

UNLABELLED: There is an urgent need to create adapted for the Russian population of the recommendations in order to improve the efficiency and automation of the process of informing patients about the correct (sanogennykh) behavior in the heat. The proposed health WHO recommendations in 2010 year are difficult to perception, understanding and subsequent patient use without consulting a doctor. THE GOAL: creating and testing adapted for the Russian population recommendations for sanogennykh behavior during the summer heat on the basis of the recommendations of the WHO in 2010. MATERIALS AND METHODS: 155 persons older than 30 years, 93 people were adapted recommendations (group 1), 62--"classic" WHO recommendations 2010 (group 2). The groups were comparable in terms of the main clinical and demographic characteristics. Results: in the summer 2014 heat waves observed 2: 4 and 10 days, the maximum temperature of 32.7 °C. On the "deterioration of health during a heat wave", complained 20.6% of patients receiving tailored recommendations, and 40%--classic (p = 0.008). The number of cardiovascular complications in group 1 was 0.0 (0.3, 1.4) in group 2--0.0 (0.6, 2.4; p = 0.000). Most effective recommendations noted patients with coronary heart disease and hypertension (87.5%; 9 of them were adapted recommendations 4--"classic") and chronic heart failure (80%; all they got adapted recommendations). CONCLUSION: customized recommendations sanogennykh behavior during heat waves can be recommended for use in clinical practice for patients with cardiovascular diseases.

[Impact of a cold wave on disease course, hemodynamics, carbohydrate metabolism, and blood rheological properties in cardiac patents].

AIM: To study the impact of cold waves on disease course, hemodynamics, lipid and carbohydrate metabolisms, oxidative stress, and blood rheological properties in patients with cardiovascular diseases (CVD). SUBJECTS AND METHODS: 24 men and 36 women (their mean age was 62.9±9.7 years) were examined; coronary heart disease (CHD) and hypertension were present in 40 and 95% of the patients, respectively; selected therapy remained unchanged throughout the entire period. The investigators measured blood pressure and pulse wave velocity (PWV), carried out biochemical blood tests, estimated plasma oxidized low-density lipoproteins (oxLDL) and malondialdehyde (MDA) and erythrocyte superoxide dismutase (SOD) activity, calculated a MDA/SOD ratio, determined blood viscosity; as well as assessed quality of life using a visual analogue scale (VAS) and a specially developed questionnaire. RESULTS: Female sex, CHD, type 2 diabetes mellitus (DM-2) were independent predictors of cardiovascular events (CVEs) in the frost period. The persons who had experienced CVEs in frost had higher baseline PWV. CVEs, such as hypertensive crisis, emergency calls, cardiac arrhythmias, and the larger number of adverse reactions, were more commonly recorded in frost. There was an increase in blood glucose levels, a decrease in oxLDL, a rise in η2/η1, and a reduction in plasma viscosity during frost and elevated glycation end product levels at visit 2. Conclusion. The cold wave is associated with the larger number of CVEs in some patients with CVD during selected therapy. CHD, DM-2, female sex are independent predictors of CVE in patients with CVD during the winter period. In this period, there were increases in the levels of glucose, glycation end products, and erythrocyte aggregation, and a reduction in plasma viscosity.

[Analysis of the state-of-the-art of consulting medical care to patients with glucocorticoid-induced osteoporosis or its risk according to the data of a questionnaire survey (GLUCOST study)].

AIM: To analyze the state-of-the-art of consulting medical care to Russian patients with glucocorticoid-induced osteoporosis (GCOP) or its risk. SUBJECTS AND METHODS: This GLUCOST study was organized and conducted by the Russian Association of Osteoporosis. A total of 1129 patients with chronic inflammatory diseases, who had been taking oral glucocorticosteroids (OGCSs) a long time (3 months or more), were examined. The patients filled out an anonymous questionnaire on their own. Whether the measures taken to diagnose, prevent, and treat GCOP complied with the main points of Russian clinical guidelines was assessed. RESULTS: 61.8% of the patients knew that the long-term treatment of GCOP might cause osteoporosis. 48.1% of the respondents confirmed the results of bone densitometry; 78.1% of the patients reported that they had been prescribed calcium and vitamin D supplements by their physician, but their regular intake was confirmed by only 43.4%; 25.4% of the patients had sustained one low-energy fracture or more. Treatment for GCOP was prescribed for 50.8% of the patients at high risk for fractures, but was actually received by 40.2%. Therapeutic and diagnostic measures were implemented in men less frequently than in women. When the patient was aware of GCOP, the probability that he/she would take calcium and vitamin D supplements rose 2.7-fold (95% Cl; 2.1 to 3.5; p = 0.001) and that he/she would follow treatment recommendations did 3.5-fold (95% Cl; 2.3 to 5.3; p = 0.001). Bone densitometry increased the prescription rate for antiosteoporotic medication and patient compliance. CONCLUSION: According to the data of Russia's large-scale GLUCOST survey, every four patients with chronic inflammatory disease who are on long-term OGCS therapy have one low-energy fracture or more. Due to inadequate counseling, the patients are little aware of their health and do not get the care required to prevent the disease. Less than 50% of patients who have GCOP and a high risk for fractures undergo examination and necessary treatment aimed at preventing fractures.

[MORPHOFUNCTIONAL MYOCARDIAL CHARACTERISTICS IN PATIENTS WITH MASKED ARTERIAL HYPERTENSION AND WHITE COAT HYPERTENSION].

The aim of this work was to study morpho-functional myocardial characteristics in patients with masked arterial hypertension (AH) and white coat hypertension (WCH) given antihypertensive therapy (AHT) and without it. This cross-sectional cohort study included employees of a large industrial enterprise who annually underwent routine medical examination supplemented by 24 hr AP monitoring and echocardiography carried out at specified time of the working day. The participants of the study were divided into 6 groups based on the relationship between clinical AP and mean AP during work. Group I comprised 20 (7%) subjects with normal AP, group 2--20 (7%) with masked AH, group 3--40 (14%) with WCH, group 4--81 (28.3%) with optimal A HT effect, group 5--64 (22.4%) with unmanifest inefficiency of AHT, group 6--40 (14%) with WCH during AHT. Criteria for masked AH and unmanifest AHT inefficiency were clinical AP below 140 and 90 mm Hg in combination with mean AP during work 135 and/or 85 mm Hg and higher. Echocardiography was performed in a standard positions in M- and B-modes as well as in three Doppler regimes. One-factor ANOVA was used to analyze differences between the groups and Pearson's Chi-square test to determine the relationship between categorical variables. 206 (72%) of the 286 employees of the large industrial enterprise had a diagnosis of AH. It was shown that ambulatory AP values obtained by 24 hr monitoring better characterized the patient's condition than clinical AP since they correlated with the frequency of disorders in the target organs and the risk of cardiovascular complications in patients with AH. Patients with masked AH more frequently developed left ventricular hypertrophy and diastolic dysfunction than those having normal clinical and ambulatory AP. The mean width of the left ventricle wall and left ventricular isovolumic relaxation time (therefore, the degree of LV hypertrophy and diastolic dysfunction) in the patients with unmanifest inefficiency of AHT were greater than in those with optimal AHT effect. The occurrence of WCH was comparable in the two groups. These data were used to determine intensity of preventive AHT at the workplace with a view to improving medical and occupational prognosis.

Genetic differentiation of Pacific cod Gadus macrocephalus in the Sea of Okhotsk and in the Bering Sea.

Genetic differentiation of the Pacific cod Gadus macrocephalus was studied. Samples from six regions of the Sea of Okhotsk and the Bering Sea were analyzed with two mtDNA genetic markers-gene of cytochrome 1 and the control region (D-loop). Comparative analysis showed significant genetic differentiation between the two groups of samples. The first group included samples from Tauiskaya Bay and waters of Western Kamchatka. The second group consisted of the samples collected in the waters of the Iturup Island (Sea of Okhotsk), Northern Kurile Islands, Navarin region of the Bering Sea, and Anadyr Bay.

[Substantiation of the choice of treatment strategy in isolated traumatic injury of the frontal lobes of the brain].

An analysis of the results of the treatment of 132 patients with isolated traumatic parenchymatous injury of the frontal lobes of the brain was made. The treatment strategy was determined in consideration of the traumatic substratum volume and a combination of neurologic status and instrumental data. There were unfavorable risk factors to the course of traumatic parenchymatous injury of the frontal lobes of the brain such as low initial GCS score, the progression of neurologic deficiency in the presence of contusion hemorrhagic foci in the frontal lobe with the volume more than 25 cm3, shifting of midline structures on 5 mm and more or signs of deformation of basilar region cisterns and the presence of mass-effect according to the tomographic data. The developed algorithm allowed improving the results of treatment and the quality of life for patients with traumatic parenchymatous injury of the frontal lobes of the brain.

[Using meldonium to improve the adaptation of patients with cardiovascular disease to the effects of heat and correction of associated oxidative stress].

Given that prolonged exposure to extreme climatic situations may play a role independent of stress factors, influencing the course of the underlying disease, the authors considered appropriate assessment of the effectiveness of additional prophylactic administration of drugs that increase the body's resistance to stress (adaptogens). The purpose of the study - to evaluate the effect of oxidative stress on meldonium, hemodynamics and quality of life of patients with cardiovascular disease (CVD) in extreme climatic conditions (summer heat). The study included 56 patients with CVD aged 38-75 years. Patients were randomized into two groups: active management (M), which in addition to basic therapy during 3 summer months received meldonium (500 mg/day), and control. The following parameters were measured: office blood pressure (BP), blood plasma malondialdehyde (MDA), erythrocyte superoxide dismutase (SOD) activity, level of oxidized low-density lipoprotein. MDA/SOD ratio was calculated. Visual analogue scale was used for assessment of quality of life. Meldonium treated patients demonstrated marked reduction of systolic BP and heart rate during heat, increased sodium level at the 2nd visit, improved quality of life. These changes corresponded to adaptive responses of healthy men. No significant dynamics of these parameters occurred in control group. MDA level during heat increased in both groups (p<0.05) but MDA/SOD ratio, which characterizes the "oxidation potential" of blood, increased significantly during the summer heat only in the control group. Meldonium can be used as an adaptogen in CVD patients during the summer heat.

[Differentiated treatment of isolated traumatic injury of frontal lobes of the brain].

An analysis of treatment results was made in 83 patients with traumatic parenchymatous injuries of frontal lobes of the brain. Surgical interventions were performed in 31 patients and the conservative therapy was carried out in 52 patients. Regular neurological examinations were completed for all the patients. The data of neurovisual methods were estimated. A strategy of treatment of frontal lobes injury depends on not only from the traumatic substratum volume, but at the same time, it is formed by clinical neurologic constellations and instrumental data in traumatic injury of frontal lobes of the brain. Risk factors of unfavorable effect of traumatic parenchymatous injury of frontal lobes of the brain were reflected in the initially low GCS score, a neurologic deficit progression with contusion haemorrhagic foci in the frontal lobe (volume greater than 25 cm3), a midline shift on 6 mm or more and signs of base cistern compression and presence of mass-effect, according to CT scan data. The developed algorithm could improve the results of treatment and makes better the quality of life of the patients with traumatic parenchymatous injuries of frontal lobes of the brain.

[The ability to use meldonium as adaptogen in winter in patients with cardiovascular disease].

Given that the effects of frost can play the role of independent stress factor influencing the course of cardiovascular disease (CVD), it is reasonable to supplementation of drugs that increase the body's resistance to cold stress. Aim: To evaluate the possibility of using meldonium to prevent unwanted seasonal changes in CVD patients in the winter. The study included 49 patients with CVD aged 38-75 years. Patients were randomized into 2 groups: active management (M), in which in addition to the basic therapy received during the winter 3 months meldonium 1000 mg/day, and a control (K). We measured office blood pressure, heart rate, blood chemistry, determination of glycosylation end products (DGP). Filled with a visual analogue scale (VAS) to assess the quality of life (QOL). During frost marked increase in blood glucose (p = 0.02) in group K, persisting throughout the winter, and an increase in tissue DGP in March (p = 0.002). In group M glucose and DGP not significantly raised. In group M at the peak of cold showed a reduction in cholesterol levels. Admission meldonium associated with improved quality of life, in the dynamics of the group K was negative [Δ +10.0 VAS scores in group M versus -7.5 points in the group K in the cold (p = 0.04) and Δ +10,0 points vs -5.0 points, respectively, in March 2014 (p = 0.055)]. Adding to the basic treatment of patients with CVD meldonium in a dose of 1000 mg/day in winter, accompanied by improved quality of life, as well as let negative changes in carbohydrate metabolism.