[Left ventricular dysfunction in patients following high-dose chemotherapy and autologous hematopoietic stem cell transplantation].

AIM: To evaluate the dynamics of LV global longitudinal strain (GLS) and other EchoCG parameters after high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation (aHSCT). MATERIAL AND METHODS: The risk of LV dysfunction in patients after HDCT followed by aHSCT has not been sufficiently studied. This study included 74 patients with hemoblastosis aged 20 to 65 years who had undergone HDCT followed by aHSCT. All patients had a history of antitumor treatment. EchoCG with assessment of LV GLS and measurements of troponin T and N-terminal pro-brain natriuretic peptide (NT-proBNP) were performed for all patients before and after the treatment. RESULTS: A decrease in GLS by 15 % or more from the baseline was detected in 6 (8.1 %) patients. The decrease in GLS was associated with increased NT-proBNP >125 pg / ml at baseline (odds ratio, 8.667; 95 % confidence interval, 1.419-52.942; p=0.022). CONCLUSION: The decrease in LV GLS in patients after aHSCT was associated with increased NT-proBNP before the intervention.

Reversible and irreversible alterations of the optical thickness of PQ/PMMA volume recording media samples. Part 2: mathematical modeling.

A theoretical study of phenanthrenequinone-doped polymethyl methacrylate (PQ/PMMA) samples parameter changes during irradiation is presented. The research has been carried out on the basis of the experimental study (Part 1, [Appl. Opt.56, 7351 (2017)APOPAI0003-693510.1364/AO.56.007351]) and a mathematical model that describes space-time reversible and irreversible light-induced changes of the PQ/PMMA sample parameters during exposition. Based on the numerical modeling results and the use of analytical dependencies, a number of practically important characteristics of the PQ/PMMA sample-exposure process are considered: conversion-induction period of phenanthrenequinone into a photoproduct, Δtind; bleaching time of a sample, tbl; and thermal nonlocality of photoresponse, δlT. It is shown that the values Δtind and tbl are on the order of tens and hundreds of seconds, respectively, and can be comparable to the exposure time. It is established that temperature increase leads to δlT value change by hundreds of nanometers and can cause considerable deformation of the interference structure under recording. The sample heating during exposition is considered in detail, and an algorithm for estimation of the maximum temperature increase to be used in experiments is proposed. Recommendations are made for the reduction of negative influence of sample heating on the parameters of recorded holograms.

Reversible and irreversible alterations of the optical thickness of PQ/PMMA volume recording media samples. Part I: Experiment.

Experimental research into changes of the optical thickness of phenanthrenequinone-doped polymethyl methacrylate samples in the process of irradiation by a 473 nm laser is presented. It was demonstrated that heating-induced reversible changes lead to a decrease in the optical thickness. The temperature coefficient of the relative changes of the optical thickness was measured to be -1.40×10-5 К-1, which matches the data published by other authors. It is also established that the irreversible changes induced by the photochemical transformation lead to an increase in the optical thickness outside of the absorption band of the samples (λ>530 nm), where the relative change of which at λ=532 nm is +3.7×10-5. It was demonstrated that the reversible and irreversible changes do not compensate for each other in the process of sample exposure.

[Microbiological monitoring of oral fluid of clinically healthy children].

The article presents qualitative and quantitative parameters of microbiocenosis of oral fluid and feces of clinically healthy children in different age groups. In most of the cases compensated disbiotic changes were found, which were characterized by reduction in the number of indigenous microflora (lactobacilli and bifidobacteria) and increase of representatives of opportunistic pathogens (Staphylococcus, Bacillus and Candida). Microecological changes in different gastrointestinal biotopes are closely interrelated. Saliva may be considered as a specimen of integral fluid of human environment and can be used for complex assessment of the state of gastrointestinal tract microflora.

Reversible photoluminescence quenching of CdSe/ZnS quantum dots embedded in porous glass by ammonia vapor.

The photoluminescence response of semiconductor CdSe/ZnS quantum dots embedded in a borosilicate porous glass matrix to exposure to ammonia vapor is investigated. The formation of surface complexes on the quantum dots results in quenching of the photoluminescence and a shortening of the luminescence decay time. The process is reversible, desorption of ammonia molecules from the quantum dot surface causes the photoluminescence to recover. The sensitivity of the quantum dot luminescence intensity and decay time to the interaction time and the reversibility of the photoluminescence changes make the CdSe/ZnS quantum dots in porous glass system a candidate for use as an optical sensor of ammonia.

Predictability of individualized dosage regimens of carbamazepine and valproate mono- and combination therapy.

WHAT IS KNOWN AND OBJECTIVE: Many investigators agree that appropriate rational utilization of therapeutic drug monitoring (TDM) with Bayesian feedback dosage adjustment facilitates epilepsy treatment with carbamazepine (CBZ) and/or valproate (VPA) by increasing the seizure control and safety, as well as by reducing treatment costs. In previous works we have developed and used in clinical practice population pharmacokinetic (PK) models of different dosage forms for VPA and post-induction CBZ behaviour, as well as for combined therapy with CBZ plus another 'old' antiepileptic drug (AED). An important step of external validation is to evaluate how well a procedure of Bayesian individualizing AED dosage regimens based on a proposed population PK model and sparse TDM data 'works', and how helpful it is in real practical clinical settings. The aim of this study was to evaluate the predictability of individualized dosage regimens for monotherapy with CBZ in the post-induction period or with VPA, as well as for CBZ and VPA given as combination therapy based on TDM data of epileptic patients and the earlier developed population models. METHODS: Four groups of TDM data were analysed using the USC*PACK software for PK/PD analysis: 556 predictions for adult epileptic patients on CBZ monotherapy, 662 predictions for VPA monotherapy, 402 predictions of CBZ serum levels and 430 predictions of VPA serum levels for adult epileptic patients on CBZ+VPA combination therapy. Statistical characteristics of the prediction errors (PE) and weighted PE were used to estimate bias and precision of predictions. Intraindividual and interoccasional variability of predictions were also estimated. RESULTS AND DISCUSSION: This study demonstrated that in most cases of CBZ and VPA monotherapy and combination therapy, predictions of future AED concentrations based on the earlier developed population PK models, TDM data and patient-specific maximum a posteriori probability Bayesian posterior parameter values provided clinically acceptable estimates. Statistical analysis of the residuals demonstrated that the distributions of residual and weighted residual were close to the normal distribution (Kolmogorov-Smirnov test, P > 0·05) and their mean values did not differ statistically significant from zero (no statistically significant bias, P > 0·05) for all groups of predictions. The observed decreased quality of predictions of VPA concentrations during VPA+CBZ combination therapy, especially when CBZ dosages were changed, might well be explained by their PK interactions. For all groups, in linear regression analysis, the observed trend of decreasing of the prediction quality over various future prediction time horizons was considered statistically significant (P < 0·05). Prediction of serum levels further in future was less precise than those closer to the present for a 1·5- to 3·5-year observation period. No bias in predictions was associated with the time horizons. WHAT IS NEW AND CONCLUSION: Our validation results suggest good predictive performance of the population models developed earlier, and quite acceptable predictions of future AED serum levels for individualized dosage regimens of CBZ and VPA therapy in real clinical settings.

[Synthesis and antituberculosis activity of the derivatives of glycoside steviolbioside from the plant Stevia rebaudiana and diterpenoid isosteviol containing hydrazone, hydrazide and pyridinoyl moieties].

Conjugates of antitubercular drug Isoniazid (hydrazide of isonicotinic acid), nicotinic and alpha-picolinic acid hydrazides and glycoside steviolbioside from the plant Stevia rebaudiana as well as the product of its acid hydrolysis, diterpenoid isosteviol, were synthesized. Besides, isosteviol hydrazide and hydrazone derivatives as well as conjugates containing two isosteviol moieties connected by dihydrazide linker were also obtained. Both initial compounds and their synthetic derivatives inhibit the growth of Mycobacterium tuberculosis (H37Rv in vitro). The minimum concentration at which the growth of M. tuberculosis was inhibited by 100% (MIC) for stevioside and steviolbioside equals 7.5 and 3.8 microg/mL, respectively. MIC values for conjugates of the hydrazides of pyridine carbonic acids and steviolbioside as well as isosteviol are in the ranges 5-10 and 10-20 microg/mL, respectively. Maximum inhibitory effect against M. tuberculosis showed the conjugates of isosteviol and adipic acid dihydrazide (MIC values ranged from 1.7 to 3.1 microg/mL). Antitubercular activity of the compounds studied is higher than the activity of antitubercular drug Pyrizanamide (MIC = 12.5-20 microg/mL) but lower than the activity of antitubercular drug Isoniazid (MIC = 0.02-0.04 microg/mL).

Sp22D: a multidomain serine protease with a putative role in insect immunity.

Serine proteases play critical roles in a variety of insect immune responses; however, few of the genes that code for these enzymes have been cloned. Here, we describe the molecular characterization of a serine protease gene from the mosquito Anopheles gambiae. Sp22D codes for a 1322 amino acid polypeptide with a complex domain organization. In addition to the carboxy terminal serine protease catalytic domain, Sp22D contains two putative chitin binding domains, a mucin-like domain, two low density lipoprotein receptor class A domains, and two scavenger receptor cysteine rich domains. A typical signal peptide sequence and a lack of potential transmembrane helices suggest that Sp22D is secreted. Sp22D is expressed constitutively in three immune-related cell types: adult hemocytes, fat body cells, and midgut epithelial cells. Wounding induces no changes in transcript abundance, but within 1h after injection of bacteria, Sp22D mRNA increases 1.5-fold. Based on domain organization, tissue distribution, and transcriptional up-regulation in response to immune challenge, we suggest that Sp22D has an immune function. In addition, we predict that Sp22D is secreted into the hemolymph where it may interact with pathogen surfaces and initiate an immune response.

Molecular characterization of five serine protease genes cloned from Anopheles gambiae hemolymph.

We identified five new serine protease cDNAs from the hemolymph of the malaria vector, Anopheles gambiae. All five show sequence similarity to genes thought to be involved in vertebrate or invertebrate defense responses. Sp14A, Sp14D2 and Sp22D demonstrate changes in transcript abundance in response to bacteria injections. Sp14A and Sp14D2, as well as the previously characterized Sp14D1, are induced by infection with the malaria parasite, Plasmodium berghei. These three proteases, along with Sp18D, are related to a group of secreted proteases that have amino-terminal clip domains and trypsin-like substrate specificity. BLAST results and phylogenetic analyses group Sp14A, Sp14D1 and Sp14D2 with the Drosophila protease EASTER, and three prophenoloxidase activating enzymes from other insects. EASTER's substrate is SPAETZLE, a ligand involved in embryogenesis but also in activating anti-microbial peptide synthesis. Their similarity to EASTER and immune inducibility suggest that one of these proteases may activate a SPAETZLE-like ligand during anti-parasite responses in mosquitoes. Alternatively, as potential prophenoloxidase activators, Sp14A, Sp14D1 or Sp14D2 may play a role in melanotic encapsulation of Plasmodium.

[The effect of dehydration dynamics on the characteristics of the E. coli cells]. / Vliianie dinamiki obezvozhivaniia na kharakteristiki bakterial'nykh kletok E. coli.

It was shown that NMR and IR-spectroscopy may be employed to study the dynamics of cell dehydration on E. coli as an example. It was noted that the withdrawal of the cell binding water causes an increase of the relative protein quantity in beta-turn. Similar dependences on the relative humidity have been obtained both for chemical shift and the changes of the secondary protein structure and the number of viable cells. It was concluded that the processes associated with binding water removal should be considered as one of the main factors, causing the inactivation of the bacterial cells.

[Central and peripheral hemodynamics in patients with essential hypertension on a fasting diet]. / Sostoianie tsentral'noi i perifericheskoi gemodinamiki u bol'nykh gipertonicheskoi bolezn'iu pri razgruzochno-dieticheskoi terapii.

Effectiveness of an antihypertensive action of fasting therapy was studied in 147 patients with arterial hypertension stage I-II. Estimation of systolic and diastolic functions of the left ventricle in patients with arterial hypertension was carried out using stress echocardiography with isometric loading. Dynamics of systolic and diastolic arterial pressure (AP) and changes in the hyperbaric index for diastolic AP were assessed at 24-h AP monitoring. The course of fasting therapy consisting of a 2-week fasting period and the recovery period of the same duration resulted in a statistically significant reduction of weight, a decrease of average daily systolic and diastolic AP, lowering of the hyperbaric index of diastolic AP and improvement of the diastolic reserve of the left ventricle. 24-h AP monitoring and stress echocardiography within 3 months showed a high clinical effectiveness of fasting therapy.

[The use of the orthostatic test in practical medical flight expertise in civil aviation]. / Ispol'zovanie ortostaticheskoi proby v praktike vrachebno-letnoi ékspertizy v grazhdanskoi aviatsii.

Comparison of results from HDT administered with different techniques showed that 5-10 min in vertical position are enough to adequately evaluate mechanisms of circulation control. By that time hemodynamic shifts get stabilized. More precise assessment of the circulation regulation can be made when HDT is administered from initial supine rather than sitting position. Analysis of the ECG dynamics allows to elicit latent myocardial injuries. The exact quantitative characteristic of orthostatic disturbances makes it possible to give their pathophysiological estimate.

[Economic stimulation as a factor of enhancing the effectiveness of health care]. / Ekonomicheskoe stimulirovanie kak faktor povysheniia éffektivnosti meditsinskoi pomoshchi.

How to achieve a higher efficiency in managing the activities of the subjects of the compulsory health insurance (CHI) system is considered in the paper. In the authors' opinion, they are, to a considerable extent, caused by the existing economic levers aimed at optimizing the activities of its main subjects such as medical service producers and purchasers. The results of introduction of economic stimulation mechanisms into practice of the CHI system are given. These mechanisms used on a specific territory may enhance the total level of efficiency of the activities of therapeutical-and-prophylactic institutions and insurers.

[Lyrica (pregabalin) in the treatment of focal refractory epilepsy in adults].

Efficacy and tolerability of a new antiepileptic drug pregabalin (lyrica) as an add-on drug in patients with focal refractory epilepsy was analyzed. The most commonly used dosage was 450 mg/d. For the 6-month treatment of 19 patients, aged 18-30 years, a positive effect of the combined therapy was observed in 68,4%, the remission was achieved in 31,6% and the significant improvement in 36,8%. Drug was discontinued due to the lack of efficacy and intolerance in 31,6%. Drowsiness was the most frequent adverse event and hemorrhagic vasculitis was registered in one patient. Two cases of effective use of the drug during pregnancy with the birth of healthy children are reported. A case of the high efficacy of pregabalin in migraine-epilepsy is described. High efficacy and good tolerability as well as favorable pharmacokinetic characteristics and distinct anxyolytic effect give indications for use of pregabalin in clinical practice.

[Dynamics of the personality profile and cognitive functions in finlepsin treatment of partial epilepsy]. / Dinamika profilia lichnosti i kognitivnykh funktsii pri lechenii partsial'noi épilepsii finlepsinom.

The aim of modern antiepileptic therapy is not only to decrease frequency of the seizures and to prevent their rise, but to decrease negative consequences of the treatment too. It is, first of all, to decrease the influence of the antiepileptic preparations on the cognitive functions and, therefore, on quality of the patients' life. During therapy of 40 patients (8-57 year-olds) with partial epilepsy the severity of the seizures as well as emotional and cognitive functions of the patients were evaluated. A significant decrease of the severity of the seizures was observed during therapy with finlepsin-retard (p < 0.002). These changes correlated both with a decrease of anxiety according to MMPI questionnaire (p < 0.0001) and with an increase of the volume of the short-term imaginary memory. Finlepsin-retard is effective therapy for epilepsy.

[Optimization of dosing of finlepsin and finlepsin-retard in patients with partial epilepsy on the basis of population modeling and drug monitoring]. / Optimizatsiia dozirovaniia preparatov finlepsin i finlepsin-retard u bol'nykh partsial'noi épilepsiei na osnove populiatsionnogo modelirovaniia i lekarstvennogo monitoringa.

Taking into account the drug monitoring data, twenty-six patients with partial epilepsy were treated with finlepsin (carbamazepin) and finlepsin-retard. According to the therapy, the patients were grouped as following: 11 patients were taking finlepsin, 10--finlepsin-retard and 5 were first treated with finlepsin and then, because of the lack of the effect, assigned to finlepsin-retard. The seizures severity was assessed using special seizures severity scale. Better clinical results (remission and reduction of seizures severity) were found in patients treated with finlepsin-retard as compared to those from other groups. Due to monitoring, a remission was reached using the lower finlepsin dosage. The authors confirm individuality of pharmacokinetic parameters, a need in precise individual treatment strategy and a necessity for controlling drug levels in plasma after replacing one form for another.

[Clinical and neurophysiological aspects of epilepsy with photosensitivity]. / Kliniko-neirofiziologicheskie aspekty épilepsii s fotosensitivnost'iu.

Using mapping EEG with dipole source location, transcranial magnetic stimulation (TMS), and visual evoked potential (VEP), clinico-neurophysiological analysis of photosensitivity was carried out in 7 patients with different types of epilepsy. In all the patients, an increase of visual response amplitude in VEP assessment and location of photogenic and eye-closing spike activity was observed in parietal and occipital areas that suggested a significant role of the striate and para striate cortex, along with primary projection cortex, in photosensitivity. Although motor cortex excitability by TMS causes hypersynchronization of the background activity and increase of slow wave discharge on the EEG after TMS. TMS is supposed to cause an activation of antiepileptic system.

[Modified screening of lung diseases in industrial workers]. / Opyt modifitsirovannogo skrininga zabolevanii lëgkikh rabochikh promyshlennykh predpriiatii.

The paper summarizes the results obtained at examination of industrial workers using a modified screening. This included questionnaires, oriented general examination, evaluation of external respiration with its monitoring during working hours. Such approach proved informative and provided a sufficient symptom complex to make diagnosis of occupational asthma.

[Radionuclide studies with a dynamic kidney phantom]. / Radionuklidnye issledovaniia s dinamicheskim fantomom pochki.

Altogether 120 studies with a dynamic kidney phantom (DKP) were conducted permitting one to imitate the normal functioning of the kidneys or different pathological states of the organ. The studies were conducted with the help of a gamma-chamber of MV-9100 type using a computer system SEGAMS (Hungary) and a chronoscope RIKh-5M-01. On completion of the experiment the activity-time curves were plotted characterizing the time course of the passage of a radioactive tracer through phantom cylinders that imitate the kidneys. The results obtained have demonstrated DKP potentialities for the imitation of various renal functional states. Studies with a DKP make it possible to select an optimum regimen for research and to assess the quality of performance of nuclear medical diagnostic equipment.