Features of Remyelination after Transplantation of Olfactory Ensheathing Cells with Neurotrophic Factors into Spinal Cord Cysts.

This paper shows for the first time that co-transplantation of human olfactory ensheathing cells with neurotrophin-3 into spinal cord cysts is more effective for activation of remyelination than transplantation of cells with brain-derived neurotrophic factor and a combination of these two factors. The studied neurotrophic factors do not affect proliferation and migration of ensheathing cells in vitro. It can be concluded that the maximum improvement of motor function in rats receiving ensheathing cells with neurotrophin-3 is largely determined by activation of remyelination.

Quantification of attenuation and speckle features from endoscopic OCT images for the diagnosis of human brain glioma.

Application of optical coherence tomography (OCT) in neurosurgery mostly includes the discrimination between intact and malignant tissues aimed at the detection of brain tumor margins. For particular tissue types, the existing approaches demonstrate low performance, which stimulates the further research for their improvement. The analysis of speckle patterns of brain OCT images is proposed to be taken into account for the discrimination between human brain glioma tissue and intact cortex and white matter. The speckle properties provide additional information of tissue structure, which could help to increase the efficiency of tissue differentiation. The wavelet analysis of OCT speckle patterns was applied to extract the power of local brightness fluctuations in speckle and its standard deviation. The speckle properties are analysed together with attenuation ones using a set of ex vivo brain tissue samples, including glioma of different grades. Various combinations of these features are considered to perform linear discriminant analysis for tissue differentiation. The results reveal that it is reasonable to include the local brightness fluctuations at first two wavelet decomposition levels in the analysis of OCT brain images aimed at neurosurgical diagnosis.

Comparative study of treatment efficacy in severe intraepithelial squamous cell lesions and preinvasive cervical cancer by conization and chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy.

BACKGROUND: Cervical cancer (CC) occupies a leading position in incidence among young women of reproductive age. In this connection, it is urgent to search for the most effective approaches to the diagnosis and treatment of this pathology. The purpose of the study was to evaluate the effectiveness of the PDT method using Cе6 with the control of the photobleaching using video and spectral fluorescence diagnostic methods, to develop the method of fluorescence-assisted systemic photodynamic therapy mediated with chlorin e6 for treatment CIN 3 and CIS. MATERIALS AND METHODS: A randomized comparative clinical study was conducted involving 94 women aged 18 to 49 years with histologically verified severe intraepithelial squamous cell lesions of the cervix or preinvasive cervical cancer. The patients were included in 2 groups: in the first group conization of the cervix was performed with curettage of the remaining part of the cervical canal; patients in the second group underwent the chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy. RESULTS: The absolute majority of patients in the main group after the first course of chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy showed normalization of cytological parameters and colposcopic picture, while women from the comparison group showed signs of cervical lesions statistically significantly more often. These changes corresponded to the dynamics of the proliferation markers expression in the cells of intraepithelial squamous cell lesions. Also, patients of the second group who were planning a pregnancy had better reproductive outcomes after treatment compared to those of the first group. CONCLUSION: In general, higher clinical efficacy and safety of the use of the chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy in the treatment of intraepithelial squamous cell lesions and preinvasive cervical cancer have been established compared to the use of standard treatment methods.

Modeling of Alzheimer's Disease to Study the Efficacy of Cell Therapy (Review).

We analyzed the main approaches to the modeling of Alzheimer's disease for studying the effectiveness of cell therapy. Recent advances in regenerative medicine in the field of neuroscience create prospects for the use of various cell preparations for the treatment of Alzheimer's disease. Experimental data on the use of neural stem/progenitor cells, mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells in various models of Alzheimer's disease are presented. Of particular importance is the standardization of protocols. The use of a standardized protocol in modeling of Alzheimer's disease will allow a comparative analysis of the effectiveness and safety of treatment to identify the optimal cell preparation. The data obtained on experimental animals can form the basis for further preclinical and clinical studies of cell therapy for Alzheimer's disease.

Application of Behavioral Tests for Evaluation of an Experimental Model of Alzheimer's Disease in Female Rats.

Alzheimer's disease was modeled in female Wistar rats aged 4 months by stereotaxic bilateral injection of a synthetic peptide ß-amyloid (Aß1-42) into the hippocampus. Behavioral tests (open field, Y-maze, passive avoidance, and Morris water maze) revealed significant impairment of memory and spatial navigation 8 weeks after ß-amyloid administration. At this term, the cognitive impairments typical of Alzheimer's disease are reproduced. The experimental model of Alzheimer's disease proposed by us can be used in preclinical studies of drugs for the treatment of this pathology.

[Morphogenetic and pathogenetic features of hypertrophic and keloid scars of the head and neck]. / Morfogeneticheskie i patogeneticheskie osobennosti gipertroficheskikh i keloidnykh rubtsov golovy i shei.

OBJECTIVE: Evaluate the morphogenetic and pathogenetic features of hypertrophic and keloid scars of the head and neck. MATERIAL AND METHODS: The study included 286 patients, among them 176 (61.5%) patients with hypertrophic and 110 (38.5%) with keloid scars aged 18 to 65 years with a disease duration from 1 month to 2 years. Material for histological and immunohistochemical (IHC) studies of scar tissue was fixed in 10% buffered formalin. Serial paraffin sections were stained with H&E, according to Van Gieson and Weigert. IHC was performed using monoclonal mouse antibodies to collagen type I (clone 3G3, Santa Cruz, dilution 1:100), collagen type III (clone B-4, Santa Cruz, dilution 1:50), collagen type IV (clone COL-94, Santa Cruz, dilution 1:50), MMP-1 (clone 3B6, Santa Cruz, dilution 1:100), α-SMA1 (clone 1A4, Dako Agilent, dilution 1:100) and rabbit polyclonal anti-TGFß antibodies (clone 3C11, Santa Cruz, 1:100 dilution). RESULTS: Pathogenetic, morphological and immunohistochemical differences in hypertrophic and keloid scars were established depending on their degree of maturity. In the formation of hypertrophic scars, the key factor in sclerotic processes is TGF-b on the background of low MMP1 activity. Keloid scars were distinguished not only by the accumulation of hard-to-degrade collagens, but also by the development of an osteoclast-like reaction with a high content of MMP1. Immature scar tissue was characterized by the presence of myofibroblastic α-SMA1 positive focus and center of inflammatory changes. CONCLUSIONS: The data obtained allow substantiating new approaches to the treatment of patients with hypertrophic and keloid scars.

Obtaining a New Gene-Cell Construct Based on Transduced Olfactory Ensheathing Cells for the Treatment of Spinal Cord Injuries.

We developed a viral vector Ad5/35-CAG-mBDNF expressing the mature form of BDNF (mBDNF). On the basis of olfactory ensheathing cells transduced with this adenovector, a new gene-cell construct was obtained. In experiments in vitro, high viability of the transduced olfactory ensheathing cells and enhanced secretion of BDNF by these cells were observed. It is possible that a new gene-cell construct will significantly increase the regenerative effects of transplanted olfactory ensheathing cells.

Neurotrophin-3 Enhances the Effectiveness of Cell Therapy in Chronic Spinal Cord Injuries.

Neurotrophin-3 enhances the effectiveness of human olfactory ensheathing cells in improving hind limb mobility in rats with post-traumatic cysts of the spinal cord. Transplantation of olfactory ensheathing cells into spinal cord cysts reduced their size; neurotrophin-3 did not modulate this effect. Combined preparation of human olfactory ensheathing cells and neurotrophin- 3 can be used in neurosurgery for the treatment of patients with spinal cord injuries.

Effect of Anesthesia on Postoperative Pain in Patients after Septoplasty.

The aim of the study was to assess acute pain syndrome in patients after septoplasty using different tactics of general anesthesia. All patients received local anesthesia with 2% procaine solution. In group 1 (95 patients), premedication with 2% promedol solution and 60 mg of ketorolac in the evening was used; group 2 (72 patients) was administered with fentanyl, propofol, cisatracuria besylate, tranexamic acid, atropine, and metoclopramide; and group 3 (89 patients) received atracuria besylate, sodium thiopental, nitrous oxide, and halothane. In groups 2 and 3, 100 mg of ketoprofen was administered intramuscularly in the evening on the day of surgery. Anterior tamponade was performed with parolon tampons in glove rubber. In groups 1 and 2, the tamponade was removed on day 2, and in group 3 it was removed 1 day after surgery. Pain syndrome was assessed on 1, 3, and 6 h and on days 1 and 2 after surgery. It was found that the scheme of anesthesia in group 2 is the most preferable, and the nasal tamponade must be removed on the 2nd day after the surgery.

Preliminary low-dose photodynamic exposure to skin cancer with chlorin e6 photosensitizer.

BACKGROUND: The study aimed to investigate the chlorin e6 photosensitizer distribution in the tumor and tumor border (5 mm) during low-dose photodynamic treatment and to increase the effectiveness of the therapy for skin neoplasms. METHODS: Sensitized boundaries of neoplasms were evaluated by video fluorescence imaging. The study of changes in the chlorin e6 distribution before/after photodynamic therapy and in the process of low-dose photodynamic exposure was carried out by the method of spectral fluorescence diagnostics. RESULTS: All 19 patients with basal-cell skin cancer had a contrast of chlorin e6 accumulation compared to normal tissues. 3 hours after intravenous administration of the photosensitizer at a dose of 1 mg/kg, the chlorin e6 concentration was: in normal tissues - 0.18 mg/kg, in the tumor - 1.26 mg/kg, in the tumor border - 0.63 mg/kg. In most cases, the fluorescence indices of chlorin e6 in tumor tissues after low-dose photodynamic therapy increased and exceeded the values before light exposure. CONCLUSION: Low-dose photodynamic therapy seems to be an optimal method for treating select skin neoplasms, which does not cause severe pain in patients during the light exposure and allows for local increase of the photosensitizer concentration in tumor tissues. This method of photodynamic therapy can improve the effectiveness of thе treatment.

The Relationship between p53-Positive Neurons and Dark Neurons in the Hippocampus of Rats after Surgical Interventions on the Nasal Septum.

The study evaluates the dependence of p53 protein expression on the appearance of dark neurons (DNs) in the hippocampus in rats during experimental modeling of septoplasty. Septoplasty simulation was carried out on 15 sexually mature male Wistar rats. We studied histological sections of the hippocampus stained with Nissl toluidine blue and antibodies to the p53 protein. In the CA1 subfield, the number of p53-positive neurons significantly increased on the 2nd, 4th (p < 0.001) and 6th days (p < 0.05). In the dynamics, the peak of the growth of p53 protein expression in the cytoplasm of CA1 and CA2 neurons fell on the 2-4th day after the operation, and on the 6th day the number of these neurons decreased (p < 0.001). In the cytoplasm of CA3 neurons in all periods after surgery, an increase in the expression of the p53 protein as compared to the control group was noted. In the CA1 pyramidal layer, the number of DNs decreased on the 6th day (p < 0.001). In CA2, after 2 days, a minimum of DNs as compared with the 4th day (p < 0.001) was noted. In CA3, on the 4th day, there was a peak in DNs as compared with the rest of the days (p < 0.001). A positive strong association was found in all periods of assessment and in all subfields of the hippocampus between an increase in the number of dark and p53-positive neurons. The appearance of dark and p53-positive neurons in the hippocampal formation in rats after simulating septoplasty are typical responses of nervous tissue to stress. It is obvious that the expression of the p53 protein is associated with the basophilia of the cytoplasm of neurons, their morpho-functional state. Presumably, the p53 protein can trigger not only the activation of damaged neurons in the hippocampus but also play a neuroprotective role. Upcoming studies should determine the role of the p53 protein in the further fate of damaged neurons in the pyramidal layer and differentiate the mechanisms of its expression.

Patient Management Strategies in Perioperative, Intraoperative, and Postoperative Period in Breast Reconstruction With DIEP-Flap: Clinical Recommendations.

BACKGROUND AND OBJECTIVE: Deep Inferior Epigastric Perforator (DIEP) flap is a tissue isolated from the skin and subcutaneous tissue of the lower abdomen or rectus muscle to foster breast reconstruction. There is limited information about DIEP-flap induced complications associated with breast reconstruction surgery. EVIDENCE: We conducted a systematic review of the published literature in the field of breast cancer reconstruction surgery. Information was gathered through internet resources such as PubMed, Medline, eMedicine, NLM, and ReleMed etc. The following key phrases were used for effective literature collection: "DIEP flap", "Breast reconstruction", "Patient management", "Postoperative DIEP", "Intraoperative anticoagulant therapy", "Clinical recommendations". A total of 106 research papers were retrieved pertaining to this systematic review. CONCLUSION: A successful breast reconstruction with DIEP-flap without complications is the priority achievement for this surgical procedure. This study provides various evidence-based recommendations on patient management in the perioperative, intraoperative, and postoperative periods. The clinical recommendations provided in this review can benefit surgeons to execute breast reconstruction surgery with minimal postoperative complications. These recommendations are beneficial to improve clinical outcomes when performing surgery by minimizing complications in perioperative, intraoperative, and postoperative period.

Low-Intensity Laser Therapy As a Method to Reduce Stress Responses after Septoplasty.

The aim of the study was to evaluate the effectiveness of the use of photobiomodulation therapy (PBMT) to minimize acute pain in the early postoperative period in patients after septoplasty. In total, 62 patients underwent septoplasty under general anesthesia (40 men and 22 women, 18-44 years old) followed by nasal tamponade. Patients of the 1st group did not undergo PBMT, and patients of the 2nd group received PBMT 3, 6, and 24 h after septoplasty (infrared pulsed laser radiation, λ = 0.890 µm, P = 10 W, 2 min in the projection of the wings of the nose). After 48 h, after the removal of tampons, intranasal PBMT with a nozzle in the red range, with λ = 0.63 µm, P = 8 mW, 2 min. ULF, HF, LF, and total power of heart rate variability (HRV), pain syndrome was assessed. ULF, LF, HF, total HRV power were significantly lower in group 2, compared to group 1. In the period from 6 to 24 h after septoplasty, patients of group 1 experienced higher pain than patients with PBMT (p < 0.001). The use of PBMT after septoplasty against the background of nasal tamponade helps to reduce the severity of pain syndrome and the inflammatory response to surgical stress and, consequently, leads to less pronounced changes in the autonomic nervous system in response to surgical stress.

The matrix-dependent 3D spheroid model of the migration of non-small cell lung cancer: a step towards a rapid automated screening.

In vitro 3D cell culture systems utilizing multicellular tumor spheroids (MCTS) are widely used in translational oncology, including for studying cell migration and in personalized therapy. However, early stages of cellular migration from MCTS and cross-talk between spheroids are overlooked, which was addressed in the current study. Here, we investigated cell migration from MCTS derived from human non-small cell lung cancer (NSCLC) cell line A549 cultured on different substrates, collagen gel or plastic, at different time points. We found that migration starts at 4-16 h time points after the seeding and its speed is substrate-dependent. We also demonstrated that co-culture of two NSCLC-derived MCTS on collagen gel, but not on plastic, facilitates cell migration compared with single MTCS. This finding should be considered when designing MCTS-based functional assays for personalized therapeutic approach and drug screenings. Overall, our work characterizes the in vitro 3D cell culture model resembling NSCLC cell migration from the clusters of CTCs into surgical wound, and describes microscopy-based tools and approaches for image data analysis with a potential for further automation. These tools and approaches also might be used to predict patterns of CTCs migration based on ex vivo analysis of patient biopsy in a 3D culture system.

Changes in the Time-Domain of Heart Rate Variability and Corticosterone after Surgical Trauma to the Nasal Septum in Rats.

The aim of the work was to study changes in the time range of heart rate variability (HRV) against the background of changes in the concentration of corticosterone in blood plasma in rats after surgical trauma to the nasal septum. Septoplasty was simulated in 30 mature male Wistar rats weighing 210-290 g. ECG was recorded with subsequent analysis of the time domain of HRV, as well as blood sampling to estimate changes in the concentration of corticosterone in the blood plasma was performed. As a result, SDNN significantly increased in comparison with the control on days 2 and 3 (p < 0.001) but decreased on days 4-5 (p < 0.001) and 6 (p < 0.01). rMSSD changed in waves with two irregular peaks on days 1 and 6. SDNN/rMSSD, in comparison with the 1st day of the postoperative period, increased on the 2nd day, continued to increase (p < 0.05), and then began to decrease on day 4 (p < 0.01). The total HRV power of was low throughout the postoperative period (p < 0.001), except for day 3, when it was equal to the control data. The increase in the total power index fell on day 3 after the operation (p <0.01), after which its decline was observed again. The concentration of corticosterone in the blood plasma in rats was significantly higher than before (p < 0.001). On postoperative day 2 to 4, its plateau was determined. Simulation of septoplasty leads to changes in the time range of HRV, an increase in the concentration of corticosterone in the blood plasma in rats with its maximum at the time of surgery and 24 h later, and the formation of a "plateau" on postoperative days 2 to 4, which coincides with the changes in HRV.

Comparison of the Effects of Septoplasty and Sinus Lifting Simulation in Rats on Changes in Heart Rate Variability.

The effects of septoplasty and sinus lifting simulation in rats on changes in the frequency domain of heart rate variability were compared. In the early postoperative period, the low-frequency component increases, and the high-frequency component decreases. The VLF range also increased. This indicates an increase in the activity of the sympathetic nervous system and a shift in metabolism under the influence of post-surgical inflammation.

[Methods of decreasing the risk of repeat interventions in patients after arterial revascularization]. / Sposoby snizheniia riska povtornogo vmeshatel'stva u patsientov posle arterial'noi revaskuliarizatsii.

Discussed in the article are the main problems related to surgical treatment of patients with peripheral artery disease, particularly taking into consideration that in the world there are from 160 to 202 million people suffering from this disease, with two thirds of such patients having signs of lesions of coronary or cerebral arteries. Vascular reconstructive interventions cannot completely eliminate the problem, since in the postoperative period there may develop cardiovascular complications related to both the limb involved as either acute or progressing chronic ischaemia and arteries of other localization (coronary, cerebral). The risk of serious cardiovascular complications in patients with a history of endured adverse ischaemic events on the part of limbs is severalfold higher. To solve these problems and decrease complications, salicylic acid is used as basic therapy. Attempts at replacing it by another drug or combined therapy with an alternative antiaggregant showed no advantages in increased risk of massive haemorrhage. On the other hand, a combination of salicylic acid with an anticoagulant at a low dose, i. e., rivaroxaban 2.5 mg twice daily as compared with acetylsalicylic acid monotherapy made it possible to significantly decrease the incidence of various cardiovascular complications in the form of myocardial infarction, stroke, adverse ischaemic events on the part of the extremity, limb amputation.

Photodynamic therapy of classic Kaposi's sarcoma with video-fluorescence control.

BACKGROUND: Kaposi's sarcoma (multiple idiopathic hemorrhagic sarcoma, Kaposi's angiosarcoma) is an angioproliferative neoplasm of endothelial origin associated with human herpes virus 8 (HHV - 8) and human immunodeficiency virus (HIV). The incidence of the classical form of Kaposi's sarcoma (КS) varies significantly in different geographical areas from 0.14/1 million people (both men and women) to 10.5 per 1 million men and 2.7 per 1 million women. The onset of КS is typical at the age of 35-39 in men and 25-39 years in women. CASE REPORT: A case of successful treatment of a recurrent non-HIV and non-HHV-8 Kaposi's sarcoma with PDT in a 79-year old man. RESULTS: After the recieved photodynamic treatment, complete pathologic response was achieved, i.e., Grade 5 tumor response according to Miller-Payne histological grading system (1999). The overall condition has significantly improved with no clinical tumor signs. CONCLUSION: This report describes a good outcome with PDT in the treatment of Kaposi's sarcoma. The results obtained are initial, but encouraging, demonstrating good tolerance, safety and high efficacy of PDT in classical КS. The successful use of PDT in cutaneous manifestations of HIV-associated KS is also described in literature.

The Effect of Transplantation of Olfactory Ensheathing Cells on the Size of Posttraumatic Spinal Cord Cysts.

We studied the effect of transplantation of ensheathing cells obtained from the olfactory mucosa of rats and humans on the size of posttraumatic spinal cord cysts. MRI examination showed that transplantation of these cells into experimental posttraumatic cysts of the spinal cord led to a significant decrease in cyst volume and even their complete disappearance in two animals receiving transplantation of rat or human cells. These findings attested to regenerative processes developing as a result of ensheathing cell transplantation. Further studies in this field will be aimed at elucidation of the mechanisms underlying spinal cord regeneration in the area of posttraumatic cysts after transplantation of ensheathing cells.

Influence of Surgical Trauma in the Nasal Cavity on the Expression of p53 Protein in the Hippocampus of Rats.

The aim of the study was to determine the role of the stress effect of septoplasty modeling on p53 protein expression in the hippocampus of rats under conditions of sensory olfactory deprivation. Simulation of septoplasty was carried out on 30 sexually mature male rats. A quantitative assessment of the apoptosis of neurons in the pyramidal layer of the hippocampus in the subfields CA1, CA2, CA3, and dentate gyrus (DG) on days 2, 4, and 6 after surgery was carried out. Histological sections were stained by the immunohistochemical method with antibodies to the p53 protein. An increase in the number of p53-positive neurons was noted in all subfields; the maximum increase in the number of apoptotic neurons was noted on day 4 after surgery. The stress effect of modeling septoplasty in rats, accompanied by sensory deprivation of the peripheral part of the olfactory analyzer, provoked the expression of p53 and the initiation of apoptosis mechanisms in various subfields of the hippocampus.