ABSTRACT
The efficacy of a new photosensitizer of chlorin E6 conjugated with a prostate-specific membrane antigen (PSMA) in photodynamic therapy of murine melanoma B16 was studied in in vivo experiments. The dynamics of photosensitizer accumulation in the tumor and surrounding tissues was evaluated and antitumor efficacy of photodynamic therapy was assessed by parameters of regression and morphological characteristics of experimental transplanted melanoma B16. The inhibitory effect of photodynamic therapy on melanoma was evaluated by complete regression of the tumor, absolute tumor growth coefficient in animals with continuation of tumor growth, and the increase in life span in comparison with the control; the criterion of cure was the absence of signs of tumor recurrence in mice within 90 days after therapy. The therapeutic potential of photodynamic therapy was determined by devitalization of tumor cells (histological examination of the zones of laser exposure on day 21 after treatment). The photosensitizer with PSMA-ligand exhibited high antitumor activity in photodynamic therapy for melanoma B16. Photodynamic therapy carried out at the optimum time after photosensitizer injection with experimentally determined parameters of laser exposure allows achieving the maximum inhibitory effect on melanoma. Pathomorphological study in the zones of exposure detected no survived tumor cells.
Subject(s)
Chlorophyllides/therapeutic use , Melanoma, Experimental/drug therapy , Photochemotherapy/methods , Skin Neoplasms/drug therapy , Urea/analogs & derivatives , Animals , Cell Line, Tumor , Chlorophyllides/chemistry , Chlorophyllides/pharmacokinetics , Female , Ligands , Melanoma, Experimental/diagnostic imaging , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacokinetics , Photosensitizing Agents/therapeutic use , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/metabolism , Skin Neoplasms/pathology , Urea/chemistry , Urea/pharmacokinetics , Urea/therapeutic useABSTRACT
Due to its nootropic, neuroprotective, and immunomodulatory effects, the peptide Semax is utilized in the treatment of ischemic stroke. Our earlier RNA-Seq analysis of the transcriptome in an ischemic model of transient occlusion of the middle cerebral artery showed an increase in the mRNA levels of many proinflammatory genes, and the suppression of their induction by Semax. However, for many relevant genes, including Il1a, Il1b, Il6 and Tnfa, the levels of their expression were too low for detailed quantitative evaluation. Here we utilize qRT-PCR to analyze the effects of the Semax peptide on the expression of weakly expressed mRNAs encoding several proinflammatory mediators, and show that exposure to Semax leads to a statistically significant decrease in the Il1a, Il1b, Il6, Ccl3, and Cxcl2 mRNAs, which compensates for the increase in the transcription of these genes induced by ischemia-reperfusion. We conclude that the observed protective effect of Semax in the model of stroke may be due to its anti-inflammatory effects. We also discuss the limitations of the RNA-Seq when applied to quantifying less abundant transcripts as compared to the real-time RT-PCR method.
Subject(s)
Brain Ischemia , Neuroprotective Agents , Pharmaceutical Preparations , Adrenocorticotropic Hormone/analogs & derivatives , Animals , Brain , Brain Ischemia/drug therapy , Brain Ischemia/genetics , Ischemia , Peptide Fragments , RNA, Messenger/genetics , Rats , Rats, WistarABSTRACT
We studied the effectiveness of photodynamic therapy with the photosensitizer Photoran E6 on the model of rat sarcoma M-1 positive for mutant p53 gene. Experiments showed that Photoran E6 exhibits high antitumor activity in photodynamic therapy of solid tumor of the connective tissue. Photodynamic therapy carried out during the optimal period after injections of Photoran E6 with the determined parameters of laser exposure allows achieving the maximum inhibitory effect on sarcoma M-1: 100% cured animals. Immunohistochemical study revealed no live tumor cells with expression of the mutant p53 protein in areas of photodynamic exposure.
Subject(s)
Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Sarcoma/therapy , Animals , Immunohistochemistry , Rats , Tumor Suppressor Protein p53/metabolismABSTRACT
The results of a complex morphofunctional study with markers of proliferation (PCNA and Ki-67), angiogenesis (CD31 and CD34), and structural integrity of mesenchymal cells (vimentin) suggest that the pool of primordial follicles was well preserved in vitrified ovarian tissue and that viability of its cellular components can be rapidly restored during incubation at 37°C within 4 h after thawing.
Subject(s)
Cryopreservation/methods , Ovarian Follicle/cytology , Ovary/cytology , Vitrification , Adult , Antigens, CD34/genetics , Antigens, CD34/metabolism , Biomarkers/metabolism , Cell Survival , Cryoprotective Agents/pharmacology , Culdoscopy , Female , Gene Expression , Humans , Ki-67 Antigen/genetics , Ki-67 Antigen/metabolism , Middle Aged , Ovarian Follicle/drug effects , Ovarian Follicle/metabolism , Ovary/drug effects , Ovary/metabolism , Platelet Endothelial Cell Adhesion Molecule-1/genetics , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Proliferating Cell Nuclear Antigen/genetics , Proliferating Cell Nuclear Antigen/metabolism , Tissue Culture Techniques , Vimentin/genetics , Vimentin/metabolismABSTRACT
Immunohistochemical and morphometric analyses have demonstrated long-distance stimulatory effects of the natural volatile components of the urine of intact mice on the proliferation of splenic lymphocytes in mice exposed to a single total γ-irradiation in a dose of 1 Gy. These results are in line with the data on stimulation of the humoral immune response to thymus-dependent antigen in irradiated mice exposed to urine specimens of intact animals.
Subject(s)
Lymphocyte Activation/drug effects , Lymphocytes/drug effects , Signal Transduction/immunology , Spleen/drug effects , Volatile Organic Compounds/pharmacology , Animals , Antibodies/immunology , Antibodies/metabolism , Biomarkers/metabolism , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Chimera/immunology , Erythrocytes/immunology , Gamma Rays , Immunization , Lymphocyte Activation/radiation effects , Lymphocytes/cytology , Lymphocytes/immunology , Lymphocytes/radiation effects , Male , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Organ Size/drug effects , Organ Size/radiation effects , Proliferating Cell Nuclear Antigen/metabolism , Sheep , Spleen/cytology , Spleen/immunology , Spleen/radiation effects , Volatile Organic Compounds/urine , Whole-Body IrradiationABSTRACT
We studied the effect of transplantation of human stem cells from various tissues on reparative processes in the brain of rats with closed craniocerebral injury. Combined treatment with standard drugs and systemic administration of xenogeneic stem cells had a neuroprotective effect. The morphology of neurons rapidly returned to normal after administration of fetal neural stem cells. Fetal mesenchymal stem cells produced a prolonged effect on proliferative activity of progenitor cells in the subventricular zone of neurogenesis. Adult mesenchymal stem cells had a strong effect on recovery of the vascular bed in ischemic regions.
Subject(s)
Brain Injuries/therapy , Mesenchymal Stem Cells/cytology , Neurons/cytology , Animals , Male , Rats , Rats, WistarABSTRACT
We studied the effects of systemic transplantation of mesenchymal stem cells obtained after culturing of autologous bone marrow on psychophysiological status of Wistar rats after diffuse brain trauma. Two months after systemic injection of mesenchymal stem cells we observed a decrease in manifestations of emotional behavioral reactions (anxiety and excitability) and shortening of the time of realization of drinking behavior in a T-maze. A significant positive effect of systemic transfusion of mesenchymal stem cells on avoidance conditioning in a shuttle box was observed 3 months after brain injury.
Subject(s)
Brain Injuries/psychology , Brain Injuries/surgery , Mesenchymal Stem Cell Transplantation/methods , Animals , Anxiety/physiopathology , Anxiety/psychology , Avoidance Learning/physiology , Behavior, Animal/physiology , Brain Injuries/physiopathology , Emotions/physiology , Male , Maze Learning/physiology , Rats , Rats, WistarABSTRACT
Effects of systemic transplantation of mesenchymal stem cells obtained by culturing of autologous bone marrow on proliferative activity of cells and functional morphology of neurons after diffuse brain injury were studied in Wistar rats. Comparative analysis of the results indicated that systemic injection of mesenchymal stem cells in a syngeneic organism produced proliferotropic, angiogenic, and, presumably, neurotrophic effects. The therapeutic effect visually manifested on day 2 after intravenous injection of mesenchymal stem cells during the early period of reparative regeneration of ischemic cell and tissue structures of the brain. The neuroprotective effect of mesenchymal stem cells was more pronounced against the background of basic therapy.
Subject(s)
Brain Injuries/therapy , Mesenchymal Stem Cell Transplantation/methods , Neurons/cytology , Animals , Brain Injuries/pathology , Cell Proliferation , Histological Techniques , Injections, Intravenous , Male , Neovascularization, Physiologic/physiology , Rats , Rats, Wistar , Transplantation, Isogeneic/methodsABSTRACT
Pronounced ultrastructural changes in vessels and mast cells were observed in duodenal lamina propria of Wistar rats 1 year after single whole-body gamma-irradiation in a dose of 7.5 Gy. Inhibition of adrenocortical function with methopyrone reduced structural damage and improved animal survival.
Subject(s)
Duodenum/blood supply , Duodenum/radiation effects , Gamma Rays , Mast Cells/radiation effects , Radiation Injuries, Experimental/prevention & control , Age Factors , Animals , Catecholamines/metabolism , Duodenum/drug effects , Duodenum/ultrastructure , Follow-Up Studies , Male , Mast Cells/drug effects , Mast Cells/ultrastructure , Metyrapone/pharmacology , Radiation Dosage , Radiation-Protective Agents/pharmacology , Rats , Rats, Wistar , Time Factors , Whole-Body IrradiationABSTRACT
Studies of the effects of vilon and epithalon on functional morphology of the thymus, spleen, and duodenum in intact rats and rats exposed to single whole-body gamma-irradiation in a dose of 6 Gy showed that vilon stimulated proliferative activity of thymocytes and enhanced proliferative potential of stem cells in the intestine, thus stimulating the postradiation recovery of critical organs. Epithalon decelerated metabolic processes in the duodenal mucosa and suppressed hemopoiesis and lymphopoiesis in the spleen.
Subject(s)
Biological Factors/pharmacology , Dipeptides/pharmacology , Duodenum/radiation effects , Oligopeptides/pharmacology , Radiation Tolerance , Spleen/radiation effects , Thymus Gland/radiation effects , Animals , Cell Division , Duodenum/cytology , Duodenum/metabolism , Duodenum/physiology , Gamma Rays , Immunohistochemistry , Male , Proliferating Cell Nuclear Antigen/metabolism , Rats , Rats, Wistar , Spleen/cytology , Spleen/metabolism , Spleen/physiology , Stem Cells/cytology , Stem Cells/radiation effects , Thymus Gland/cytology , Thymus Gland/metabolism , Thymus Gland/physiologyABSTRACT
Immunohistochemical and morphometric analysis showed that epithalamin and epithalon produced similar effects on the functional morphology of the spleen in pinealectomized rats. Both peptides prevented hyperplasia of lymphoid cells in follicular germinative centers induced by pinealectomy and potentiated the decrease in extramedullary hemopoiesis. These findings confirm the data on functional relationships between the pineal gland and immune system. The effects of epithalamin and epithalon on cell and tissue homeostasis in the spleen of old pinealectomized rats can be regarded as a manifestation of the general regulatory effect of these peptides.
Subject(s)
Oligopeptides/pharmacology , Peptides/pharmacology , Pineal Gland/metabolism , Spleen/drug effects , Animals , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Immunohistochemistry , Male , Necrosis , Proliferating Cell Nuclear Antigen/pharmacology , Prostaglandins/metabolism , Rats , Rats, Wistar , Spleen/metabolism , Spleen/pathology , Time FactorsABSTRACT
Endocrine cells in the stomach of pinealectomized rats after injection of epithalone (pineal gland peptide) were studied by immunohistochemical tests, morphometry, and image analysis microscopic images. A functional relationship was found between the pineal gland and stomach, which is regulated by peptides produced by the pineal gland.
Subject(s)
Gastric Mucosa/drug effects , Neuropeptides/pharmacology , Oligopeptides/pharmacology , Pineal Gland/physiology , Animals , Endocrine Glands/cytology , Endocrine Glands/drug effects , Endocrine Glands/physiology , Gastric Mucosa/cytology , Gastric Mucosa/physiology , Gastrins/metabolism , Immunohistochemistry , Male , Rats , Rats, Wistar , Somatostatin/metabolismSubject(s)
Mast Cells/physiology , Melatonin/physiology , Neoplasms, Experimental/physiopathology , Neoplasms, Experimental/radiotherapy , Radiation Tolerance/physiology , Animals , Cell Hypoxia/drug effects , Cell Hypoxia/radiation effects , Histamine H1 Antagonists/pharmacology , Humans , In Vitro Techniques , Ketotifen/pharmacology , Mast Cells/drug effects , Models, Biological , Serotonin/physiologyABSTRACT
The paper presents a review of the results obtained by the authors on the study of external (gamma) and internal (I-131) radiation effects on the functional morphology and linkage of the diffuse neuroendocrine system (DNES) and amine precursor uptake and decarboxylation (APUD) cells of the stomach and duodenum. The investigations performed enabled us to determine that the morphological changes noted in APUD cells had a dose and time dependency. The present study supports the point of view that the radiation initiates serotonin release from APUD cells, which appears to initiate the mechanism of early postirradiation dysfunctions of the gastrointestinal tract and the subsequent adaptive response of DNES. Analysis of our results, together with a review of the literature, indicates that APUD cells actively participate both in pathogenesis of radiation injury and development of organ and tissue radiosensitivity.
