Photosensitizing effects and physicochemical properties of chlorophyll a derivatives with hydrophilic oligoethylene glycol fragments at the macrocycle periphery.

In this work, screening studies of the cytotoxic effect of chlorins with fragments of di-, tri-, and pentaethylene glycol at the macrocycle periphery in relation to HeLa, A549, and HT29 cells were performed. It is shown that, despite different hydrophobicity, all the compounds studied have a comparable photodynamic effect. The conjugate of chlorin e6 with pentaethylene glycol, which has the lowest tendency to association among the studied compounds with tropism for low density lipoproteins and the best characteristics of the formation of molecular complexes with Tween 80, has a significant difference in dark and photoinduced toxicity (ratio IC50(dark)/IC50(photo) approximately 2 orders of magnitude for all cell lines), which allows to hope for a sufficiently large "therapeutic window". A study of the interaction of this compound with HeLa cells shows that the substance penetrates the cell and, after red light irradiation induces ROS appearance inside the cell, associated, apparently, with the photogeneration of singlet oxygen. These data indicate that photoinduced toxic effects are caused by damage to intracellular structures as a result of oxidative stress. Programmed type of cell death characterized with caspase-3 induction is prevailing. So, the conjugate of chlorin e6 with pentaethylene glycol is a promising antitumor PS that can be successfully solubilized with Tween 80, which makes it suitable for further in vivo studies.

[ACTUAL STRATEGY OF TREATMENT VARICOSE VEINS RECURRENCE AFTER ENDOVENOUS INTERVENTIONS].

The aim of the study is to substantiate the surgical treatment tactics of recurrence varicose veins after endovenous interventions. Early and long-term results of the treatment, quality of life of patients with recurrence of varicose veins were studied. Among the admitted patients, there were 55 (65.5%) women and 29 (34.5%) men, the age of patients varied from 19 to 76 years. Of these, 9 patients underwent crossectomy, endovenous laser coagulation - 22, various stripping options - 4, echosclerotherapy - 20, intraoperative catheter sclerobliteration - 1, ligation of perforating veins - 28 patients. The choice of the treatment method depends on the data of duplex angioscanning, the source of recurrence, the diameter and length of the varicose veins. In the early postoperative period 18 (22.6%) patients had complications and side effects. Most often hyperpigmentation and neurological disorders developed, which were observed in 8 (9.5%) and 7 (8.3%) cases. 2 (2.4%) patients had a slightly painful dense cord after endovenous laser coagulation. 1 (1.2%) patient had a lymphocele in the inguinal incision area. This complication was eliminated by use of the puncture treatment method. Long-term results in terms of 1 to 3 years were studied in 82 (97.6%) patients. In the long-term period, 1 (1.2%) patient noted the varicose veins recurrence due to neovasculogenesis in the groin. The patient underwent micro-foam echosclerotherapy. Patient`s quality of life was studied by using the CIVIQ2 questionnaire before and 1 year after treatment. It was found that 4 main indicators of the quality of life in the long-term period improved by 35.6-48.8% of the preoperative values. At the same time, the most significant positive dynamics of psychological (48.8%) and pain (47.1%) factors was observed. The results justify the need for a differentiated approach, taking into account the individual characteristics of the disease, as well as the expediency of using minimally invasive techniques in patients with varicose veins recurrence.

NECROTIC FASCIITIS AS A COMPLICATION OF ACUTE DESTRUCTIVE APPENDICITIS.

The timely diagnosis of necrotic fasciitis (NF) - an extremely rare fatal complication of acute appendicitis is difficult due to the variability of the clinical picture and depends on the degree of inflammatory changes in the appendix wall, localization, age, reactivity, and the presence or absence of comorbidities. It is characterized by high mortality rate, associated with the rapid progression of the disease with the development of septic shock and multiple organ failure. A clinical case of necrotic fasciitis of the right lower limb without damage of the anterior abdominal wall, secondary to the perforated process, as an extremely rare complication of appendicitis is presented. A 78-year-old patient was urgently operated on laparoscopically for acute gangrenous appendicitis. Necrotic fasciitis has not been diagnosed. Ten hours after the operation, the diagnosis of NF was established and the patient underwent phlegmon autopsy of the right thigh and lower leg, revision of the retroperitoneal space on the right. Subsequently, sanitation and surgical treatment of purulent foci were performed. Despite the ongoing comprehensive treatment in the intensive care unit using broad-spectrum antibiotics the disease progressed, and wet gangrene of the right lower limb developed. The patient underwent amputation at the level of the upper third of the right thigh. The course of the disease was complicated by sepsis, septic shock, bilateral pneumonia, multiple organ failure syndrome, cerebral edema. The patient died on the 8th day from the moment of hospitalization. The rarity of this formidable and fatal disease determines the difficulties of early diagnosis and timely treatment, since most doctors can see one case of NSTIs throughout their medical career. Our case shows how important the early diagnosis of this fatal complication is, as it is crucial for achieving optimal treatment results.

; RESULTS OF RESECTION METHODS OF TREATMENT IN PATIENTS WITH GIANT PYLORODUODENAL ULCERS COMPLICATED BY PERFORATION AND BLEEDING.

We studied the immediate and long-term results of various methods of gastric resection in 35 patients operated at the S.S. Yudin State Medical Center in Moscow from 2000 to 2019. 20 (57.1%) patients were operated on for perforation, and 15 (42.6%) patients underwent surgery for ulcerative bleeding. There were 27 (77.2%) males and 8 (22.8%) females. The average age of patients was 48.3±2.3 years. The diagnosis of peptic ulcer disease was previously made in 24 (68.6%) patients, the duration of the disease was 7.7±2.7 years. Of the 35 patients, 29 (82.8%) underwent standard gastric resection without vagotomy with Billroth-II anastomosis in various modifications and 6 (17.2%) underwent pylorobulbar resection with Billroth-I anastomosis with bilateral stem vagotomy. According to the analysis of the results of surgical interventions, gastric resection was accompanied by a significant number of early postoperative complications observed in 18 (51.4% of patients): associated with the nature of the operation, 10 and 5 patients had complications from the cardiovascular and respiratory systems. The most frequent complication due to the nature of surgery was a clinically significant violation of the evacuation function of the stomach stump, which developed in 8 of 35 (22.8%) patients. In 4 patients after pylorobulbar resection, the violation of the evacuation function of the stump was due to its parasympathetic denervation. The remaining 4 patients after standard resection of gastric stasis stump occurred due to maintenance of anastomositis of gastrojejunal anastomosis. Post-vagotomic diarrhea: observed in 3 of 6 patients: 1 patient of moderate severity, and 2 patients-mild. Failure of sutures was observed in 2 out of 35 (5.7%) patients after standard gastric resection: one after resection of Hofmeister Finsterer and the other after resection for PY. Complications from the cardiovascular system were observed in 5 (14.3%) patients. After surgery, 5 (22.7%) patients died: 4 after resection of 2/3 of the stomach and 1 patient after pyloroduodenal resection with stem vagotomy. All the deceased were operated on urgently: 2 patients for perforation of giant ulcers and 3 patients for continuing profuse bleeding. The causes of death of patients operated on for bleeding were: myocardial infarction in 1 patient, pulmonary embolism in 2 patients. Another 2 patients with failure of duodenal stump sutures, operated on for perforation of giant ulcers, died from increasing cardiovascular insufficiency. The analysis of long-term results of surgical interventions showed a steady decrease in the number of post gastric resection and post-vagotomic disorders, as well as the absence of ulcer recurrence. It should be noted that the phenomena of dumping syndrome observed in patients after standard gastric resection were not severe and were corrected by a lax diet. After piloroduodenal resection with anastomosis by Billroth-I and stem vagotomy, manifestations of gastrostasis and diarrhea were stopped in the remote postoperative period. When assessing the quality of life, there were no unsatisfactory results, all previously operated patients led their usual lifestyle, maintained their working capacity, and did not require re-hospitalization.

[The use of apparent diffusion coefficient in diagnosis of lumbar intervertebral disk degeneration in patients with middle and old age by diffusion-weighted MRI.]

The most common cause of low back pain is the intervertebral disk (IVD) degeneration. Standard modes of MRI (T1 and T2-modes) do not allow quantifying the degree of IVD degeneration. Diffusion-weighted MRI (DW MRI) is able to analyze the state of IVD structures by the diffusion of water molecules. The degree of diffusion can be estimated using the apparent diffusion coefficient (ADC). In this paper, a quantitative assessment of the degree of IVD degeneration was made by ADC calculating. 281 IVD were studied in 57 elderly and senile patients with the definition of body mass index (BMI). ADC values and degree of C.W.Pfirmann degeneration were measured. For each of the five IVDs, reliable differences in mean ADC values were determined. Between age and mean ADC values noted inverse relationship. Between the degree of IVD degeneration, BMI and ADC values, a reliable inverse relationship noted also. Age, BMI values and the degree of IVD degeneration are the most significant factors affecting the ADC value. Thus, the DW MRI technique can be recommended, as a modern non-invasive method for diagnosing the degree of IVD degeneration in elderly and senile patients.

Assessment of Lactate Production and Proteoglycans Synthesis by the Intact and Degenerated Intervertebral Disc Cells under the Influence of Activated Macrophages: an In Vitro Study.

The effects of proinflammatory cytokines on the secretion of glycosaminoglycans and lactate production by normal and degenerated intervertebral disk cells were studied on the model of their co-culturing with activated macrophage-like cells. It was found that proinflammatory cytokines produced a direct effect on intervertebral disk cells in a 3D culture reducing the rate of glycolysis and synthetic activity of both normal and degenerated cells of annulus fibrosus and nucleus pulposus, which is an important factor in progression of intervertebral disk degeneration.

Development of an In Vitro Model of Inflammatory Cytokine Influences on Intervertebral Disk Cells in 3D Cell Culture Using Activated Macrophage-Like THP-1 Cells.

We developed a new model for evaluation of the influence of proinflammatory cytokines on intervertebral disc cells in a 3D culture based on co-culturing of these cells with activated macrophage-like THP-1 cells. The levels of TNFα, IL-1ß, IL-6, IL-8, IL-10, and IL-12p70 production were assessed by flow cytofluorometry using microspheres. Considerable differences in the level of spontaneous cytokine secretion by normal and degenerated intervertebral disc cells were revealed. A significant increase in the level of IL-1ß and IL-8 was observed during co-culturing, which confirms consistency of the developed model.

Complex Analysis of Diffusion Transport and Microstructure of an Intervertebral Disk.

We studied the relationship between diffusion transport and morphological and microstructural organization of extracellular matrix of human intervertebral disk. Specimens of the lumbar intervertebral disks without abnormalities were studied ex vivo by diffusion-weighed magnetic resonance imaging, histological and immunohistochemical methods, and electron microscopy. Distribution of the diffusion coefficient in various compartments of the intervertebral disk was studied. Significant correlations between diffusion coefficient and cell density in the nucleus pulposus, posterior aspects of annulus fibrosus, and endplate at the level of the posterior annulus fibrosus were detected for each disk. In disks with nucleus pulposus diffusion coefficient below 15×10-4 mm2/sec, collagens X and XI were detected apart from aggrecan and collagens I and II. The results supplement the concept on the relationship between the microstructure and cell composition of various compartments of the intervertebral disk and parameters of nutrient transport.

[Molecular biology of brain meningiomas].

Meningiomas are by far the most common tumors arising from the minges. A myriad of aberrant signaling pathways involved with meningioma tumorigenesis, have been discovered. Understanding these disrupted pathways will aid in deciphering the relationship between various genetic changes and their downstream effects on meningioma pathogenesis. An understanding of the genetic and molecular profile of meningioma would provide a valuable first step towards developing more effective treatment for this intracranial tumor. Chromosomes 1, 10, 14, 22, their associated genes, have been linked to meningioma proliferation and progression. It is presumed that through an understanding of these genetic factors, more educated meningioma treatment techniques can be implemented. Future therapies will include combinations of targeted molecular agents including gene therapy, si-RNA mediation, proton therapy, and other approaches as a result of continued progress in the understanding of genetic and biological changes associated with meningiomas.

[The possibilities for diagnostics of prescription of death coming based on the changes in the lumbar intervertebral disks (the comparison of the morphological, immunohistochemical and topographical findings)]. / Vozmozhnosti diagnostiki davnosti nastupleniia smerti po izmeneniiam v poiasnichnykh mezhpozvonkovykh diskakh (sopostavlenie morfologicheskikh, immunogistokhimicheskikh i tomograficheskikh rezul'tatov).

The objective of the present study was the comprehensive analysis of the postmortem changes in the lumbar intervertebral disks within different periods after death. A total of seven vertebromotor segments were distinguished in the lumbosacral region of the vertebral column based on the examination of 7 corpses. All these segments were divided into three groups in accordance with the prescription of death coming as follows: up to 12 hours (group 1), between 12 and 24 hours (group 2), and between 24 and 36 hours (group 3) after death. The models of the segments thus obtained were subjected to the study by means of diffusion weighted MRI. The removed intervertebral disks were used for morphological and immunohistochemical investigations. The comparison of the diffusion coefficients (DI) revealed the significant difference between the intervertebral disks assigned to groups 1 and 2 (p<0.01). The number of the cells in the pulpal core, the vertebral end plate, and the fibrous ring in all the above groups of the intervertebral disks was significantly reduced (p<0.01). The analysis of the correlation dependence between cell density and diffusion coefficients has demonstrated the well apparent relationship between these characteristics of the intervertebral disks comprising groups 1 and 2. It is concluded that diffusion weighted MRI in the combination with the calculation of diffusion coefficients for the intervertebral disks provides a tool for diagnostics of prescription of death coming as confirmed by the results of the morphometric studies and immunohistochemical analysis.

[Simulation technologies in spinal surgery].

This review reflects the current state of simulation technologies in neurosurgery and, in particular, in spinal surgery. Currently, there are different types of simulations used in spine surgery including the biological, artificial and virtual models. Simulations help to facilitate an optimal study of the anatomy, understand the spatial relationships between organs and tissues, plan properly the surgical intervention, and gain tactile surgical skills. The implementation of simulation technologies in the educational process provides objective assessment of the initial level of training, improvement of the competence in trained professionals, as well as prevention of surgical errors in various clinical situations.

[The Use of Stem Cells in the Treatment of Intervertebral Disc Degeneration].

The paper presents a review of current data on the use of stem cells in the treatment of intervertebral disc degeneration. Acute spinal pain is often a consequence of the pathology affecting the intervertebral disc. Many applied therapeutic techniques do not provide effective results as expected because most of them address symptoms, but do not treat the underlying disease. We have outlined current findings on the molecular mechanisms of intervertebral disc degeneration, analyzed international experimental studies demonstrating the feasibility of a stem cell therapy for intervertebral disc degeneration. The conducted studies reported on the clinical application of mesenchymal stem cells or stem cells derived from adipose, synovium, and bone marrow tissue. The most pressing and undetermined issues that require further experimental and clinical studies are indicated and defined in the article.

[Facet Fixation Combined with Lumbar Interbody Fusion: Comparative Analysis of Clinical Experience and A New Method of Surgical Treatment of Patients with Lumbar Degenerative Diseases].

Background: For the treatment of patients with degenerative diseases of the lumbar spine the technique of pedicle fixation is widespread, when after open decompression channel structure locking screws are introduced into the vertebral body through the back vertebra legs. We first used a fundamentally new way of fixing the rear using the facet-boards Cage «Facet Wedge¼, when posterior fixation is done by closing the facet joints with minimally invasive, percutaneous method. We have not found data on the clinical efficacy of facet fixation in scientific literature. Aims: To compare the clinical efficacy of facet fixation combined with interbody fusion in the treatment of patients with degenerative lumbar spine disease. Materials and Methods: The study included 145 patients who were divided into 2 groups. The study group with long-term observation included patients (n=100) who underwent a new method for lumbar fixation; the method comprises unilateral or bilateral implantation of titanium Cage «facet Wedge¼ in the joint space facet joint in combination with the anterior, lateral, and transforaminal interbody fusion. Clinical comparison group (n=45) included retrospectively recruited patients who were performed titanium pedicle screw installation after open decompression and interbody fusion posterior lumbar fixation. Dynamic observation and comprehensive evaluation of the treatment clinical results was carried out for 18 months after surgery. Results: Cage facet installation technology is quite simple, universal for the stabilization of the rear of the complex after interbody fusion from the front, side, and rear access; and does not require the intraoperative application of expensive high-tech equipment. Comparative analysis of the main group showed significantly better results in terms of the duration of the operation [CG 125 (90; 140) min, the CCG 205 (160; 220) min; p=0.01], the volume of blood loss [CG 80 (70; 120) ml, CCG 350 (300; 550) ml; p=0.008], activation time [CG 2 (1; 2) days, 4 CCG (3; 5) days; p=0.02], length of hospitalization [CG 9 (10; 11) days, the CCG 13 (12; 15) days; p=0.03], the level of pain on a visual analog scale [CG 3 (2; 4) mm, CCG 15 (12; 18) mm; p=0.001], quality of life (by index Oswestry) [CG 8 (6; 8) points, the CCG 23 (20; 28) points, p=0.003], and labor rehabilitation [CG 3 (2; 6) months, CCG 9 (6; 12) months; p=0.0001]. The number of postoperative complications in group 1 was 13%, in the 2nd ­ 31,1% (p=0,0012). The new method involves fixing the back with considerably less surgical trauma of paravertebral soft tissue that results in early activation of patients, reduction of stay in hospital period, and better functional recovery of patients. Conclusions: The application of facet fixation combined with interbody fusion in the treatment of patients with degenerative diseases of the lumbar spine allows achieving the best clinical outcomes and fewer postoperative complications during the short and long-term follow-up if compared with the traditional method of transpedicular stabilization. The combination of low-impact and reliability facet fixation techniques for posterior stabilization of the operated segment creates favorable conditions for the restoration of a functional condition of patients, full social and physical rehabilitation.

[New simulation technologies in neurosurgery].

The article presents a literature review on the current state of simulation technologies in neurosurgery, a brief description of the basic technology and the classification of simulation models, and examples of simulation models and skills simulators used in neurosurgery. Basic models for the development of physical skills, the spectrum of available computer virtual simulators, and their main characteristics are described. It would be instructive to include microneurosurgical training and a cadaver course of neurosurgical approaches in neurosurgery training programs and to extend the use of three-dimensional imaging. Technologies for producing three-dimensional anatomical models and patient-specific computer simulators as well as improvement of tactile feedback systems and display quality of virtual models are promising areas. Continued professional education necessitates further research for assessing the validity and practical use of simulators and physical models.

[Cytogenetic effects in Allium schoenoprasum growing on the anthropogenically contaminated soil].

Cytogenetic effects in Allium schoenoprasum meristematic root tip cells grown for a year on the territory contaminated with 235U, 238U and 232Th decay series radionuclides, heavy metals and As were studied. The area is characterized with different concentrations of chemical compounds in soil affecting a toxic element migration in biocoenosis. Analysis of the chromosome aberration spectrum showed an ambiguous cell response to soil contamination. Within the weighted absorbed dose range up to 1.2 Gy the higher the dose the aberrant cell frequency increase was shown. But further increase in the dose resulted in a genotoxic effect decrease due to high toxic effects of heavy metals and radionuclides in soil. This was registered as a mitotic index decrease that can provoke a chromosome aberration frequency underestimation and result in erroneous conclusions about genotoxic effects in A. schoenoprasum used as a bioindicator.

[The level of DNA damage and DNA reparation rate in cells of earthworms sampled from natural populations for numerous generations inhabited territories with anthropogenically enhanced levels of radionuclides in soil].

Low doses of ionizing radiation and chemical toxic agent effects on biological systems on different organization levels have been studied by numerous researchers. But there is a clear lack of experimental data that allow one to reveal molecular and cellular adaptations of plants and animals from natural populations to adverse effects of environmental factors. The present study was aimed to assess genotoxic effects in earthworms Aporrectodea caliginosa Savigny and Lumbricus rubellus Hoffmeister sampled from the populations that during numerous generations inhabited the territories with a technogeneously enhanced content of natural origin radionuclides and heavy metals in soil. The levels ofthe DNA damage detected with alkaline and neutral versions of Comet-assay in invertebrates from contaminated territories were established not to differ from the spontaneous level found in the animals from the reference population. At the same time the rate of the DNA damage reparation induced in A. caliginosa sampled from the contaminated sites with additional acute γ-irradiation (4 Gy) was found to be considerably higher as compared with earthworms from the reference population.

[Genetic diversity of the locus COI-COII of mitochondrial DNA in honeybee populations (Apis mellifera L.) from the Tomsk region].

An assessment of the genetic diversity of the COI-COII mtDNA locus in honeybee populations from the Tomsk region was conducted. Three variants of the COI-COII mtDNA locus were registered: PQQ, PQQQ (typical for Middle Russian race), and Q (typical for southern breeds). It was established that 64% of bee colonies of the maternal line originate from the Middle Russian honeybee race, 28% of bee colonies originate from southern species, and 8% are mixed bee colonies. The southern parts of the region show a higher genetic diversity of honey bees as compared to northern regions, which are dominated by bee colonies (96%) and apiaries (73%) that are homogeneous for the genetic variant of locus COI-COII. The Tomsk region has no large areas with bee colonies maternally originating from the Middle Russian breed; only a few apiaries (both in the northern and southern areas) were revealed in which all bees originated from the Middle Russian breed.

Nanostructure changes in the intervertebral discs after experimental laser irradiation.

Laser-induced changes in the intervertebral discs were studied by the method of atomic force microscopy. Alteration of the proximal caudal intervertebral discs was modeled in rats: puncture and exposure to diode laser (2, 3, or 5 W) in constant or pulse regimens or only puncture (control). Nanostructure of disc surface was estimated by surface skewness, root mean square and average roughness, and coefficient of kurtosis. Maximum positive effect and signs of regenerative changes in the surface microstructure of the intervertebral discs were found after exposure to laser (2-3 W) in constant or pulse regimens.

[CLINICAL EFFECTIVENESS OF PUNCTURE METHODS FOR THE TREATMENT OF VERTEBRAL BODY FRACTURES AND HEMANGIOMAS].

UNLABELLED: A new stenoplastic technology including implantation of expanding titanium cage is realized to improve the quality of life and relieve pain syndrome in the patients with injured vertebral bodies. The aim, of the study was to compare clinical effectiveness of puncture vertebroplasty and stenoplasty. MATERIALS AND METHODS: Vertebroplasty and stenoplasty were used in 24 and 18 cases respectively to treat 17 patients with A1 compression fractures of vertebral bodies and 25 ones with symptomatic hemangiomas in thoracic and lumbar spine. Visual-analog scale was used to estimate severity of pain syndrome, ODI scale to assess the quality of life, and Macnab scale to evaluate satisfaction of the patients with the results of surgery; in addition, duration of surgery and frequency of complications were determined. RESULTS: Results of hemangioma treatment by both procedures were similar when estimated by VAS and ODI (p < 0.05). Stentoplasty yielded better long-term results of the treatment of A1 compression fractures based on VAS and ODI (p = 0.03) and should be preferred over vertebroplasty Also, this technique can be used to treat symptomatic hemangiomas.

[EPIDURAL HEMATOMA WITH SPINAL CHORD COMPRESSION ASSOCIATED WITH WARFARIN INTAKE].

The most serious life-threatening warfarin-associated complications is hemorrhage in CNS structures. Reports of spontaneous spinal epidural hematomas in patients using warfarin, methods of diagnostics and treatment are but few. We describe the first case of warfarin-associated spontaneous spinal epidural hematoma in this country and a literature review of this issue.