Hydroxycobalamin catalyzes the oxidation of diethyldithiocarbamate and increases its cytotoxicity independently of copper ions.

It is known that some metals (Cu, Zn, Cd, Au) markedly increase the toxic effect of thiocarbamates. It was shown in the present study that hydroxycobalamin (a form of vitamin B12, HOCbl), which incorporates cobalt, significantly enhances the cytotoxicity of diethyldithiocarbamate (DDC), decreasing its IC50 value in tumor cells three to five times. The addition of HOCbl to aqueous DDC solutions accelerated the reduction of oxygen. No hydrogen peroxide accumulation was observed in DDC + HOCbl solutions; however, catalase slowed down the oxygen reduction rate. Catalase as well as the antioxidants N-acetylcysteine (NAC) and glutathione (GSH) partially inhibited the cytotoxic effect of DDC + HOCbl, whereas ascorbate, pyruvate, and tiron, a scavenger of superoxide anion, had no cytoprotective effect. The administration of HOCbl into DDC solutions (> 1 mM) resulted in the formation of a crystalline precipitate, which was inhibited in the presence of GSH. The data of UV and NMR spectroscopy and HPLC and Mass Spectrometry (LC/MS) indicated that the main products of the reaction of DDC with HOCbl are disulfiram (DSF) and its oxidized forms, sulfones and sulfoxides. The increase in the cytotoxicity of DDC combined with HOCbl occurred both in the presence of Cu2+ in culture medium and in nominally Cu-free solutions, as well as in growth medium containing the copper chelator bathocuproine disulfonate (BCS). The results indicate that HOCbl accelerates the oxidation of DDC with the formation of DSF and its oxidized forms. Presumably, the main cause of the synergistic increase in the toxic effect of DDC + HOCbl is the formation of sulfones and sulfoxides of DSF.

Evaluation of Regenerative Potential of Cryopreserved Adenosine-Modified Monocytes on the Model of Burn Wounds.

We studied viability of adenosine-modified monocytes after cryopreservation and their regenerative potential. The optimal method of cell cryopreservation was the use of serum-free medium followed by storage in liquid nitrogen. Injections of adenosine-modified monocytes after 12-week cryopreservation around grade IIIB burn wound accelerated healing of the skin defect and significantly improved the histological pattern of the damage area at delayed terms.

Investigation of TbMn2O5 by polarized neutron diffraction.

In order to make a new approach to the elucidation of the microscopic mechanisms of multiferroicity in the RMn2O5 family, experiments with different methods of polarized neutrons scattering were performed on a TbMn2O5 single crystal. We employed three different techniques of polarized neutron diffraction without the analysis after scattering, the XYZ-polarization analysis, and technique of spherical neutron polarimetry (SNP). Measurements with SNP were undertaken both with and without external electric field. A characteristic difference in the population of 'right' and 'left' helix domains in all magnetically ordered phases of TbMn2O5, was observed. This difference can be controlled by an external electric field in the field-cooled mode. The analysis of the results gives an evidence that antisymmetric Dzyaloshinsky-Moria exchange is effective in all the magnetic phases in TbMn2O5.

[How necessary to perform neoadjuvant chemoradiotherapy for rectal cancer in geriatric patients?]

A comparative analysis of the efficacy and safety of neoadjuvant chemoradiotherapy (CRT) in colorectal cancer patients older and younger than 60 years has been performed. It was determined that the risk of complications of neoadjuvant CRT, as well as the degree of its adverse effect on outcomes after surgical treatment, are not significant for the age of patients. However, the use of preoperative CRT in elderly patients is associated with a less significant increase in recurrence-free survival in comparison with younger patients. Thus, the age factor should not limit the use of neoadjuvant CRT in patients with satisfactory general status and the absence of severe complications of the pathological process.

Analysis of Gut Microbiota in Patients with Parkinson's Disease.

Gut microbiota of patients with Parkinson's disease and healthy volunteers was analyzed by the method of high throughput 16S rRNA sequencing of bacterial genomes. In patients with Parkinson's diseases, changes in the content of 9 genera and 15 species of microorganisms were revealed: reduced content of Dorea, Bacteroides, Prevotella, Faecalibacterium, Bacteroides massiliensis, Stoquefichus massiliensis, Bacteroides coprocola, Blautia glucerasea, Dorea longicatena, Bacteroides dorei, Bacteroides plebeus, Prevotella copri, Coprococcus eutactus, and Ruminococcus callidus, and increased content of Christensenella, Catabacter, Lactobacillus, Oscillospira, Bifidobacterium, Christensenella minuta, Catabacter hongkongensis, Lactobacillus mucosae, Ruminococcus bromii, and Papillibacter cinnamivorans. This microbiological pattern of gut microflora can trigger local inflammation followed by aggregation of α-synuclein and generation of Lewy bodies.

Low temperature magnetic structure of CeRhIn5 by neutron diffraction on absorption-optimized samples.

Two aspects of the ambient pressure magnetic structure of heavy fermion material CeRhIn5 have remained under some debate since its discovery: whether the structure is indeed an incommensurate helix or a spin density wave, and what is the precise magnitude of the ordered magnetic moment. By using a single crystal sample optimized for hot neutrons to minimize neutron absorption by Rh and In, here we report an ordered moment of [Formula: see text]. In addition, by using spherical neutron polarimetry measurements on a similar single crystal sample, we have confirmed the helical nature of the magnetic structure, and identified a single chiral domain.

Implementation of a new Cryopad on the diffractometer POLI at MLZ.

A new polarized neutron single crystal diffractometer POLI (Polarization Investigator) has been developed at the Maier-Leibnitz Zentrum, Garching, Germany. After reviewing existing devices, spherical neutron polarimetry has been implemented on POLI as a main experimental technique using a third-generation cryogenic polarization analysis device (Cryopad) built in cooperation between RWTH University and Institut Laue-Langevin. In this report we describe the realization and present the performance of the new Cryopad on POLI. Some improvements in the construction as well as details regarding calibrations of Cryopad and its practical use are discussed. The reliable operation of the new Cryopad on POLI is also demonstrated.

Biological Collections: Chasing the Ideal.

This article is based on the results of an analysis of existing biological collections in Russia and abroad set up in the framework of the project "Scientific Basis of the National Biobank -Depository of Living Systems" by M.V. Lomonosov Moscow State University [1].

CYTOREDUCTIVE OPERATIONS IN TREATMENT OF THE PATIENTS OF ELDERLY AND SENILE AGE WITH DISSEMINATED FORMS OF COLORECTAL CANCER.

Late diagnostics of colon cancer along with high specific weight of the patients of elder age groups indicated the urgency of study of application of cytoreductive surgery in elderly and senile patients of with colorectal cancer. A comparative assessment of the results of cytoreductive operations (primary tumor resection) was made in two groups of patients with disseminated colon cancer (younger and older than 60 years old). It was stated, that the performance of palliative resection allowed them to obtain of encouraging remote results, provide more higher survival rates than in patients of young and mean age groups. The more frequent development of complications after cytoreductive operations was associated with decompensation of accompanying pathology in patients of elder age groups. These data confirmed the need of their adequate correction in preoperative period. The application of cytoreductive surgery significantly improved the quality of life of the patients of elder age groups with disseminated forms of colon cancer.

[Application of GLAD-PCR analysis for the methylation sites detection in the regulatory areas of tumor-suppressor genes ELMo1 and EsR1 in colorectal cancer].

Aberrant methylation of regulation regions of tumorsuppressor genes is showed for many cancer diseases. In course of this modification an enzyme DNMT3 methylates RCGY sites in CpG-islands of regulation regions producing R(5mC)GY sites. Earlier we developed GLAD-PCR assay to determine R(5mC)GY site in a definite position of human genome. In this work we have applied GLAD-PCR assay to determine R(5mC)GY sites in regulation regions of ESR1 and ELMO1 tumor-suppressor genes. We have studied a fragment of first exon of ELMO1 gene and a part of ESR1 promoter region in DNA preparations from malignant cell line SW837 and colorectal tumor samples. We have checked four sites in each region and found two highly methylated sites: GCGC in first exon of ELMO1 gene and GCGT in promoter region of ESR1 gene. Site GCGT is weakly methylated in healthy tissues and more methylated in the most of colorectal samples. Site GCGC is not methylated in healthy tissues and significantly methylated in 60% of colorectal samples. A possibility to use GLAD-PCR assay for cancer diagnostics is discussed.

SURGICAL TREATMENT FOR PATIENTS OF ELDERLY AND SENILE AGE WITH LOCALLY ADVANCED COLON CANCER.

The article analyzed the results of radical operative treatment of 102 patients aged 35-85 years old. It was shown that combined operations on patients of 60 years old and older were associated with high risk of somatic complications in postoperative period. However, these operations provided more higher rate of survival compared with patients younger than 60 years old and improved the quality of life.

[Geriatric aspects in oncocoloproctology (review)].

Severe comorbidity significantly limits the use of active surgical tactics in patients of older age groups suffering from colorectal cancer (CRC), leading to the abandonment of the necessary operations in 20 % of cases. The low use of radical surgical tactics are not always related to objective difficulties, but often can be due to the stereotypical approach to solving the question of the treatment of the elderly patient, which leads to unreasonable refusal of surgical intervention. Today is not defined by a single concept of surgical treatment of patients with colon cancer in elderly and senile age. There is no universally accepted system for determining the functional operability in this group of patients, not developed specific algorithms for their preoperative preparation and perioperative management. In this regard, the search for new approaches to surgical treatment of geriatric patients with CRC, allowing, on the one hand, to increase the percentage of completion radical surgery, and on the other, to reduce the number of postoperative complications in this numerous group of patients, is one of the priority tasks of Oncology.

[Correlation Between Emotional-Affective Disorders and Gut Microbiota Composition in Patients with Parkinson's Disease].

Background: Despite the efforts of scientific community the data available on the correlation between emotional-affective symptoms of Parkinson's disease and changes in microbiome is still scarce. Deeper studies of nonmotor symptoms evident in premotor stages of the disease and the reciprocal influence of microbiota may help to understand the etiology and pathogenesis of PD neurodegeneration better. Aim of the Study: Discover the relations between emotional-affective disorders prevalent in PD population and changes in gut microbiota composition. Methods: 51 patient diagnosed with PD participated in the study. Every participant's emotional-affective state was examined using Beck's Depression Inventory (BDI) and Hospital Anxiety and Depression Scale (HADS). Taxonomic richness of microbiome was studied using 16S ribosomal RNA gene sequencing, bioinformatics, and statistical analysis. Results: Anxiety and depression are prevalent affective disorders in patients with PD. In our study, most of the subjects demonstrated certain anxiety and depression. Taxonomic diversity of gut microbiota in BP was increasing with the increase in anxiety levels, reaching the maximum in the group with subclinical anxiety, and decreasing in the group with clinically significant anxiety disorder. At the species level, patients with clinically significant anxiety had higher abundance of Clostridium clariflavum compared to the anxiety-free patients. Patients with moderate depression were characterized by the higher prevalence of Christensenella minuta, Clostridium disporicum, and Oscillibacter valericigenes compared to subjects without depression or with mild depression. Conclusion: The data we received in our study allow better understanding of PD pathogenesis.

[Clinical and Functional Phenotypes of Chronic Obstructive Pulmonary Disease, the Effect on the Severity of the Disease and Prognostic Value in Assessing the Risk of Disease Progression].

Background: Chronic obstructive pulmonary disease (COPD) is characterized by progressive limitation of airflow rate, hyperergic inflammatory response of the respiratory tract, and systemic manifestations. Prognosis of the disease depends on the severity of these pathogenetic components. FEV1 which characterizes the speed limit airflow do not allow predicting the rate of COPD progression. Aims: Comparison of the prognostic significance of such clinical parameters as frequency of exacerbations and the development of comorbid diseases to assess the nature of COPD progression by using different classification approaches. Materials and Methods: The prospective comparative study included 98 patients with COPD. In the framework of the study protocol, 2 visits were required when a practitioner recruited patients who met inclusion/exclusion criteria, obtained the signed informed consent, collected the anamnestic data, and performed basic procedures of the study: spirometry, 6-minute stepper test, assessment of dyspnea on questionnaire mMRC, body plethysmography, lung diffusion capacity study, dopplerechocardiography, tomography of the chest. Visit 2 was conducted in 12 months after the first one to assess the dynamics of the disease. The dynamics of the disease was considered negative if, upon repeated examination, the patient was referred to the group with more severe COPD. Results: Our study demonstrates that comprehensive assessment of such factors as the frequency of COPD exacerbations in the preceding 12 months and the presence of comorbid diseases in a patient is reasonable for assessment of disease severity and determination of disease prognosis. At the same time the frequency of COPD exacerbations as one of the evaluated factors is most strongly associated with disease progression. Conclusions: Thus, a practitioner is recommended to use the proposed additional clinical criteria to assess the severity and degree of progression of COPD.

[Clinico-functional phenotypes of chronic obstructive pulmonary disease, their influence on the severity of the disease, and prognostic value for risk evaluation].

Attempts at optimizing classification of chronic obstructive pulmonary disease (COPD) reflect clinical heterogeneity of this pathology and provide a basis for the search of new phenotypic markers (especially at the early stages of the disease) that could be useful for prognostication of its severity in individual patients. One of the potential makers is phenotyping of COPD with distinguishing bronchitic, emphysemic, and mixed phenotypes. This paper presents results of analysis of functional characteristics of the patients with these phenotypes. They are shown to reflect clinical and functional features of the disease that may be of value for diagnostic purposes, the choice of the treatment strategy and prognosis of the outcome in individual patients.

[PREVENTIVE COLOSTOMY IN PLANNED TREATMENT OF PATIENTS WITH RECTAL CANCER].

The article described an original method of forming preventive colostomy, which reduced the rate of incompetence of interintestinal anastomosis in sphinctersaving resection concerning rectal cancer. This also facilitated patient's rehabilitation in early postoperative period.

[THE CHARACTERISTICS OF SYSTEMIC AND LOCAL IMMUNE REACTIONS UNDER HABITUAL NON-CARRYING OF PREGNANCY].

The study was carried out to evaluate clinical informativeness ofstudies of immunological parameters of structural and functional elements of endometrium in complex with profile of embritropic autoimmune antibodies under non-carrying of pregnancy The sampling consisted of 19 women of reproductive age with episodes of non-carrying in first semester. They were examined for inherited thrombophilia and profiles of immune reactivity of natural regulatory auto-antibodies (ELI-P-Complex). The biopsy material of endometrium was subjected to histological and immune histochemical (CD16, CD56, CD68, CB138, estrogen and progesterone receptors) analyses. In women with non-carrying of pregnancy polyclonal immunosuppression, increased level of embriotoxic auto antibodies to Fc- fragment of immunoglobulin, insulin and thyroglobulin are detected. The immune histochemical analysis established expressed decreasing of amount of progesterone receptors of stromal elements of endometrium after spontaneous abortion. The activation of killer activity of decidual lymphocytes under habitual non-carrying of pregnancy was detected too. The positive dependency was established between: expression of progesterone receptors in glandular cells of endometrium and level of anti-spermatic antibodies in blood serum; expression of progesterone receptors in stroma and level of antibodies to human chorial gonadotropin; expression of receptors of estrogens in stroma and level of antibodies to Fc-fragment of immmunoglobulines. The study data permits affirming that evaluation of level of regulatory auto-antibodies is informative at examination of woman after episode of non-carrying of pregnancy. The production of antibodies has direct relationship with pathological processes in endometrium and it can be one of criteria of completeness of pre-conceptional preparation.

[The efficacy of peptide bioregulators of vessels in lower limbs chronic arterial insufficiency treatment in old and elderly people].

Atherosclerosis is a leading cause of obliterating diseases of the arteries in 80-90% of cases. The main pathogenetic mechanism is endothelial dysfunction, leading to hypertension, diabetes, congestive heart failure. The desire of modern society to improve the quality of life increases interest of human health in general and sexual health in particular, because the erectile function is an important factor in the quality of life, which makes us look for more effective methods of diagnosis, treatment and rehabilitation. The objective of the study was to assess the effectiveness of vasoactive tripeptide Vezugen in patients with vasculogenic erectile dysfunction as manifestation of atherosclerosis. Treatment results of erectile dysfunction in 41 patients were studied. A comparative analysis of clinical and instrumental parameters of blood flow in the main penile arteries before and after monotherapy was undertaken. The results show that the blood flow through the main artery of the penis after Vezugen treatment significantly improved both clinical and by objective indicators.

[Stimulation of adenosine receptors on myeloid cells enhance leukocyte migration at the site of burn injury].

Adenosine, endogenous purine nucleoside, is an ATP metabolite that also acts as an extracellular signaling molecule. The concentration of extracellular adenosine rises during hypoxia and cell damage leading to numerous pleiotropic effects. Although a high concentration of adenosine was found at burn injury, the effect has not been well elucidated. We have studied human peripheral blood myeloid cell, due to their expression of specific adenosine receptors and capacity to migrate to the site of burn injury. We have shown that myeloid cells after 72 hours of stimulation of adenosine receptors develop altered expression of surface antigens: preserved monocyte's marker CD14 with already expressed dendritic cell markers (CD209, CD1a). Whereas untreated cells have already lost monocyte marker in 72 hours, and express CD1a more abundantly. Adenosine modified myeloid cells express also higher levels of mRNA of proinflammatory cytokines and chemoattractants (IL-6, IL-8, IL-1 b). Using mouse model of the burn injury we have shown, that adenosine modified bone marrow derived myeloid cells injected in the site of the injury promote migration of granulocytes, monocytes, macrophages, and fibroblasts on the 7th day after burn. Thus, stimulation of adenosine receptors alters differentiation and function of myeloid cells. In the site of burn injury adenosine modified myeloid cells augment cell migration due to paracrine factors.

[The reagents kit to detect Metyorchis biis, Opisthorchis viverrini and Clonorchis sinensis, Opisthorchis felineus--agents of opisthorchiasis using technique of polymerase chain reaction in real-time].

The helminths Opisthorchis felineus, Opisthorchis viverrini, Clonorchis sinensis, Metorchis bilis are the agents of opisthorchiasis. The actual diagnostic of parasitic diseases based on microscope analysis of samples of human feces to detect presence of ova of parasites suffers of many shortcomings, in particular low sensitivity especially at earlier stages. The purpose of this study was to compare results of detection of parasites using both classical technique and technique of specific differentiation based on extraction of nucleic acids from samples of human feces and implementation of reaction of amplification of the chosen fragment of DNA with detection of products of polymerase chain reaction in the real time. The study detected 150 out of 165 positive samples and also 6 out of 37 negative samples both validated by coproovoscopy.