Исследование острой токсичности монокатионного производного хлорина е6 – перспективного фотосенсибилизатора для антимикробной и противоопухолевой фотодинамической терапии

In this experimental work the acute toxicity of a chemically modified derivative of the natural pigment chlorophyll a called monocationic chlorin e6, which is a promising photosensitizer (PS) for antimicrobial and antitumor photodynamic therapy, was studied using white rats. The advantages of the PS under investigation are an intense absorption in the long-wavelength region of the visible spectrum, a sufficiently high quantum yield of singlet oxygen generation, pronounced amphiphilic properties along with an appropriate solubility in water, and a high level of photocytotoxic- ity in relation to both malignant HeLa cells and antibiotic-resistant hospital strains of E. сoli bacteria., P. aerugenosa and others. It has been shown that the value of LD50 of the considered PS can be calculated as the value of 100 mg/kg. In the reproduced experimental model of acute toxicity, pathomorphological changes in the vital organs of laboratory animals indicate a pronounced vasopathic effect of the drug with the development of cerebral edema and respiratory distress syndrome, which have become the main signs of thanatogenesis.На белых крысах изучены особенности острой токсичности химически модифицированного производного природного пигмента хлорофилла а монокатионного хлорина e6 – перспективного фотосенсибилизатора (ФС) для антимикробной и противоопухолевой фотодинамической терапии. Преимуществами ФС являются интенсивное поглощение в длинноволновой области видимого спектра, достаточно высокий квантовый выход генерации синглетного кислорода, выраженные амфифильные свойства наряду с хорошей растворимостью в воде и высокий уровень фотоцитотоксичности в отношении как злокачественных клеток линии HeLa, так и антибиотикорезистентных госпитальных штаммов бактерий E. coli, P. Aerugenosa и других. Величина ЛД50 для монокатионного хлорина e6 составляет 100 мг/кг массы тела. В воспроизведенной экспериментальной модели острой токсичности патоморфологические изменения жизненно важных органов лабораторных животных свидетельствуют о выраженном вазопатическом действии препарата с развитием отека головного мозга и респираторного дистресс-синдрома, ставшими основными звеньями танатогенеза

CLINICAL OUTCOMES OF PERCUTANEOUS CORONARY INTERVENTION WITH DRUG ELUTING STENT IN STABLE ANGINA PATIENTS

Aim. To evaluate the occurence of cardiovascular events (CVE) and influence of lipid parameters on it, as other clinical and instrumental factors of coronary heart disease (CHD) patients during 5 years after selective percutaneous coronary intervention (PCI) with drug eluting stenting (DES).Material and methods. In the study, 574 patients included, with stable angina (81% males, mean age 60,3 y. o.), hospitalized to the FSBI RCSPC of MHRF for selective PCI with implantation of DES. Patients were prescribed the therapy according to stable angina guidelines, including statins. The analysis was done, of various clinical and instrumental and laboratory parameters for evaluation of prognostic significance. The endpoints were assessed: lethal cases from cardiovascular, as from all causes, non-fatal myocardial infarction (MI), non-fatal stroke, repeated coronary revascularization, that happened after discharge.Results. During the entire follow-up (average 53,5 months), CVE were registered in 24% cases. Totally, died 29 patients (5,1%), of those 4 (0,7%) — from non-cardiac causes, and repeat revascularization was done in 84 (14,6%) patients, non-fatal MI and stroke developed in 17 (3,0%) and 8 (1,3%), respectively. The risk factors were defined, that are related with the rate of fatal outcomes: smoking, brachiocephalic atherosclerosis, stroke in anamnesis, significant lesion of circumflex artery (CA) and its branches. Non-fatal stroke developed more oftenly in patients with higher body mass index (BMI) (32,2±2,56 versus 28,15±4,22, p=0,0164). Non-fatal MI more oftenly registered in patients with higher number and length of implanted stents (p=0,0018 and p<0,0001, resp.). By the end of follow-up, there were 66,2% patients on statins treatment. Target low density lipoproteides cholesterol (LDL-C) level (<1,8 mM/L) was found in 8,7%, median LDL-C level was 2,8 mM/L. There were no significant differences in LDL-C between those taking statins and discontinued,during 5 years. There was no significant relation of lipid profile values with CVE as well. The number of fatal cases was higher in the group of patients with lower baseline high density lipoproteide cholesterol. Conclusion. Adverse events were found in about quarter of patients. Most of patients did not reach the target LDL-C. There was no significant relation in baseline LDL-C and its level in 5 years, with the occurence of MI, stroke, repeat revascularizations, all cause deaths. This can be explained by the absence of significant differences in LDL-C levels in patients continuing and discontinued statins during the follow-up, and is related to the use of insufficient statins dosages and low adherence to statin treatment

Application of artificial neural networks in studying the dynamic structure of the near-Earth orbital space

A description of the technique for studying the dynamic structure of the near-Earth orbital space using machine learning technology is presented. Artificial neural networks were used to process time series associated with the evolution of resonance characteristics that determine the dynamic structure of the near-Earth region up to 120 thousand km along the semi-major axis. The number of the processed series has exceeded half a million, and their manual processing would be time consuming. The results of applying the technique to the analysis of the resonant structure of the selected area of space are presented

A single-electron reducing quinone oxidoreductase is necessary to induce haustorium development in the root parasitic plant Triphysaria

Parasitic plants in the Orobanchaceae develop haustoria in response to contact with host roots or chemical haustoria-inducing factors. Experiments in this manuscript test the hypothesis that quinolic-inducing factors activate haustorium development via a signal mechanism initiated by redox cycling between quinone and hydroquinone states. Two cDNAs were previously isolated from roots of the parasitic plant Triphysaria versicolor that encode distinct quinone oxidoreductases. QR1 encodes a single-electron reducing NADPH quinone oxidoreductase similar to zeta-crystallin. The QR2 enzyme catalyzes two electron reductions typical of xenobiotic detoxification. QR1 and QR2 transcripts are upregulated in a primary response to chemical-inducing factors, but only QR1 was upregulated in response to host roots. RNA interference technology was used to reduce QR1 and QR2 transcripts in Triphysaria roots that were evaluated for their ability to form haustoria. There was a significant decrease in haustorium development in roots silenced for QR1 but not in roots silenced for QR2. The infrequent QR1 transgenic roots that did develop haustoria had levels of QR1 similar to those of nontransgenic roots. These experiments implicate QR1 as one of the earliest genes on the haustorium signal transduction pathway, encoding a quinone oxidoreductase necessary for the redox bioactivation of haustorial inducing factors

Isolation, identification, and chromatographic separation of N-methyl derivatives of glycoluril

Mono-, di-, and tetramethylglycolurils were synthesized, isolated, and purified. For the first time, the cis- and the trans-isomers of N,N-dimethylglycoluril were isolated as individual substances by semi-preparative HPLC method. The structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR, and HR–HPLC–MS. The EI mass spectra of individual substances were obtained by the GC–MS. Retention and resolution of N-methyl glycolurils were investigated in the reversed-phase HPLC mode for different stationary phases: C18, SB–Aq, and Luna 5u PFP(2). The retention of N-methyl glycolurils depended on the amount of CH3 groups and distance between the CH3 groups in the structure. The stationary phases provided different selectivity for glycoluril and its N-methyl derivatives due to different shape selectivity. Complete separation of the N-methyl derivatives of glycoluril was achieved in 4.5 min on the stationary phase with pentafluorophenyl propyl ligand in a gradient mode

DIAGNOSTIC PROBLEMS OF MUCOVISCIDOSIS AND WAYS OF SOLUTION IN RUSSIA

Mucoviscidosis is a monogenic autosomal recessive caused by the CFTR gene mutations and characterized by pronounced genetic heterogeneity and clinical polymorphism, which emphasizes the need in comprehensive diagnosis and molecular-genetic verification of the final diagnosis. Quality and duration of a mucoviscidosis patient depend on early diagnosis and timely adequate therapy. The article presents mucoviscidosis diagnostic methods and protocols and capabilities of the modern molecular-genetic pathological diagnosis; a review of DNA diagnostic sets has been performed. As sets of some of the genes typical to the Russian population have not been registered in the Russian Federation, mutations in 20% of the patients cannot be specified. In order to solve this problem it is necessary to develop DNA diagnostic sets specific for the Russian Federation, ensure genetic diagnosis of the disease, including sequencing methods at the expense of the federal budget, increase the amount of information and improve quality of teaching this discipline to  students of medial universities and at postgraduate courses for appropriate specialists