Photodynamic Therapy of Melanoma B16 with Chlorin E6 Conjugated with a PSMA-Ligand.

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.

Effect of Vitrification on Functional Morphology and Viability of the Ovarian Tissue.

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.

Stimulatory effect of volatile urinary components from intact mice on the proliferative activity of splenic lymphoid tissue in irradiated animals.

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.

Effect of cell therapy on recovery of cognitive functions in rats during the delayed period after brain injury.

We studied the effect of systemic transplantation of human stem cells from various tissues on cognitive functions of the brain in rats during the delayed period after experimental brain injury. Stem cells were shown to increase the efficacy of medical treatment with metabolic and symptomatic drugs for recovery of cognitive functions. They accelerated the formation of the conditioned defense response. Fetal neural stem cells had a stronger effect on some parameters of cognitive function 2 months after brain injury. The efficacy of bone marrow mesenchymal stem cells from adult humans or fetuses was higher 3 months after brain injury.

[Immunohistochemical and ultrastructural characteristics of papillary carcinoma of the thyroid in people living in regions contaminated with radionuclides]. / Immunogistokhimicheskaia i ul'trastrukturnaia kharakteristika papilliarnogo raka shchitovidnoi zhelezy u lits, prozhivaiushchikh v raonakh s radionuklidnym zagriazneniem.

Papillary thyroid carcinoma was studied in 12 patients who lived in the radionuclide polluted and nonpolluted areas. Neither immunohistochemical nor EM differences in the structure of the carcinoma between the contaminated and non-contaminated regions were found. Three structural variants were identified: classical, follicular and mixed, immunohistochemically having follicular-cell differentiation. Three EM types of cell were observed: dark, clear and intermediate.

[The effect of vincristine on the morpho-functional state of the rat small intestine]. / Vliianie vinkristina na morfofunktsional'noe sostoianie tonkoi kishki krys.

The effect of vincristine treatment on the morphofunctional status of the small intestine was studied morphologically in 80 Wistar rats. The drug was found to possess a general toxic effect. Diarrhea was matched by the arrest of crypt cell-proliferation at metaphase, lysis, a decreased disaccharidase activity and increased levels of cytoplasmic alkaline phosphatase and dipeptidyl(amino)peptidase-IV in enterocytes of the villi. Exudation and degenerated cell organellae prevailed in intramural nervous ganglion cells, smooth muscle cells of intestinal tunica muscularis and vessels and in endothelium. The said changes were transitory in epithelium, but never regressed in nervous structures. At later stages (6-12 months after vincristine, but never regressed in endothelium. The later stages (6-12 months after vincristine treatment), secondary dystrophic changes developed in the small intestine wall, being predominantly confined to neuromuscular and vascular elements.

Combined exposure to electrochemical lysis and photodynamic therapy.

A combination of electrochemical lysis and photodynamic therapy were used to attain complete resorption of M-1 sarcoma in rats; both treatment modalities were used with minimum parameters. Fotolon served as the photosensitizer for photodynamic therapy. Accumulation of the sensitizer in the tumor and normal tissue was evaluated before photodynamic therapy. Complete resorption of sarcoma in 100% cases (vs. photodynamic monotherapy) was attained only by the following treatment protocol: fotolon injection 50 min before electrochemical lysis (10 min) followed by photodynamic therapy. No tumor tissue was detected in morphological sections.

Evaluation of antitumor efficiency of electrochemical lysis on the model of M-1 sarcoma.

Antitumor efficiency of electrochemical lysis was evaluated on the model of M-1 sarcoma. At stage 1 of the study, the results of therapy with electrodes in different position were compared, at stage 2 various combination of electrochemical lysis parameters (current strength and duration of exposure) were evaluated. The increase in parameters was associated with the increase in the percentage of cases with complete regression of tumors, which was confirmed by morphological data.

Morphofunctional study of the therapeutic efficacy of human mesenchymal and neural stem cells in rats with diffuse brain injury.

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.

Morphofunctional study of the therapeutic effect of autologous mesenchymal stem cells in experimental diffuse brain injury in rats.

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.

[Protective and repair processes in the small intestine during radiation exposure]. / Zashchitnye i vosstanovitel'nye protsessy v tonkoi kishke pri radiatsionnom vozdeistvii.

The small intestine as a complex heterostructural organ possesses morphofunctional defence-regenerative mechanisms. All elements of this mechanism suffer in irradiation of the organ especially at ionizing radiation doses causing the acute intestinal syndrome. Regenerative processes in the small intestine are suppressed not only by ionizing radiation but also by the toxic products of exo- and endogenous origin resulting from irradiation of the body.

[Ultrastructural changes in the proper layer of the mucous membrane of the duodenum following general gamma-irradiation]. / Ul'trastrukturnye izmeneniia v sobstvennom sloe slizistoi obolochki dvenadtsatiperstnoi kishki pri obshchem gamma-obluchenii

The work has been performed on mature male Wistar rats which were irradiated in a "Gamma-Sell-220" apparatus in the dose of 1000 r, with thepower 42 r/sec. It has been shown that in early terms after irradiation (1-6 hours) slightly pronounced destructive changes were observed in cellular and fibrous structures of the stroma of theproper layer of the duodenum membrane in addition to pronounced exudative changes. Further, the latter increased and became maximum within 24 hours. The edema extends into the basal part of enterocytes and between the stroma cells giving rize to desorganization of all mucous membran elements. Seventy two hours after irradiation the destructive changes in cellular and fibrous structures of the mucous membrane layer proper became predominant. The authors make a conclusion that the changes in the stroma aggravate dysfunction of the epithelium injured by the irradiation energy.

[Enzymes in the mucosal layer of the small intestine]. / Fermenty sloia slizi tonkoi kishki.

It has been demonstrated by the methods of histochemical and biochemical examination of the activity of the enzymes that the mucus layer covering the small intestinal wall contains active enzymes (alkaline phosphatase, leucin aminopeptidase IV, saccharase, lactase) and pancreatic enzymes (alpha-amylase and trypsin). Emphasis is laid on the enrichment of the mucus layer with pancreatic enzymes as compared with small intestinal juice. A hypothesis has been advanced according to which the mucus layer undergoes degradation of polymeric and oligomeric substrates, which plays a physiological part in the digestion of nutritive substances and protection of the internal medium against immunoactive biopolymers. The digestion occurring in the mucus layer is proposed to be called mucus digestion.

[Effect of peritol on the functional and morphological characteristics of the small intestine in rats]. / Vliianie peritola na funktsional'nye i morfologicheskie kharakteristiki tonkoi kishki krys.

Experiments were made on 140 male Wistar rats with the use of morphological, biochemical and radiometric research methods. It was established that as soon as the treatment with the anabolic drug peritol was completed, there appeared the morphological signs attesting to an increase in functional activity of vasculostromal elements of the small intestine, and the absorption rate of vitamin B12 got intensified. Activity of enzymes responsible for parietal digestion (alkaline phosphatase, invertase), absorption of 59Fe-citrate and 131I-albumin were unchanged. No substantial changes were revealed on the part of the morphology and function of the small intestine in the long-term period after peritol administration.

Diffuse neuroendocrine system: structural and functional effects of radiation injury to amine precursor uptake and decarboxylation (APUD) cells.

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.