Electron microscopic characteristic of local immune processes during regression of developed experimental tumors under the influence of magnetite nanoparticles.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14179-e14179
Author(s):  
Galina V. Zhukova ◽  
Oleg I. Kit ◽  
Marina I. Bragina ◽  
Tatiana N. Gudtskova ◽  
Alla I. Shikhlyarova ◽  
...  

e14179 Background: Previously, regression of the developed transplanted tumors under the influence of magnetite nanoparticles (NPs) as monofactor was shown. The purpose of the study was to reveal signs of intercellular interactions in the zone of tumors regressed under the influence of magnetite NPs. Methods: Experiments were carried out on 14 white outbred male rats (180-200 g) with transplanted sarcoma 45 of an initial volume of 0.7-1.3 cm3. After 6 peritumoral injections of magnetite NPs (10 ± 2 nm) in the form of magnetic fluid AM-01 ("AM-Kub", Ekaterinburg) twice a week in a single dose of 17.7 mg/kg, 5 out of 7 rats of the main group demonstrated a regression of the tumor from 1.5-3 cm3 to 0.7 ± 0.2 cm3 (in the control group – 9.7 ± 1.9 cm3, p < 0.01). Ultrathin sections of the tumor tissue of 12 animals (including 7 rats of the main group) were examined in electron microscope JEOL JEM-1011 (Japan). Results: Under effective action of magnetite NPs in tumor tissue, in addition to necrosis, apoptosis and autophagy were marked. In the case of apoptosis, chromatin condensation in compact masses and separation of apoptotic bodies were observed. Significantly more common autophagic cell death was identified by violation of the integrity of the cell membrane and the presence of autophagosomes. Numerous signs of activation of cell-cell interactions with participation of immune cells were observed. Diverse groups of 2-4 contacting cells included macrophages, lymphocytes, plasmocytes, degranulated mast cells, neutrophils in various combinations with distinct signs of the metabolic activity. Invagination of macrophages cytoplasm into the cytoplasm of tumor cells, close adjacency of the cytoplasmic membranes of neutrophils and lymphocytes at considerable length, tight intertwining of mast cell cytoplasmic processes and engulfing of the mast cell granules by macrophages were noted. Conclusions: The results supplement the characteristics of immune processes during the self-dependent antitumor action of magnetite NPs.

2010 ◽  
Vol 12 (3) ◽  
pp. 327-333 ◽  
Author(s):  
Baki S. Albayrak ◽  
Ozgur Ismailoglu ◽  
Konuralp Ilbay ◽  
Umut Yaka ◽  
Gamze Tanriover ◽  
...  

Object Epineural fibrosis may complicate peripheral nerve surgeries and currently is considered as one of the main factors responsible for failed surgeries. The authors investigated the postoperative antiscarring effects of topically applied doxorubicin (DXR) on rat sciatic nerves. Methods The sciatic nerves were dissected from the surrounding tissue and exposed bilaterally in 20 Wistar albino adult male rats. Abrasion trauma was produced on the exposed surface of the biceps femoris muscle in the vicinity of the sciatic nerves and their main branches in all animals. In the DXR Group, cottonoid pads soaked with DXR (0.5 mg/ml) were placed around the nerves for 5 minutes, whereas cotton pads soaked with saline (0.9% NaCl) were applied to nerves of animals in the Control Group for the same duration. Twelve weeks after the procedure, all of the rats were killed and the sciatic nerves were examined. Epineural adhesions were evaluated histopathologically and ultrastructurally. Additionally, quantitative histological parameters, the scar tissue formation index and the scar density, were calculated in histological evaluation. Results Gross postsurgical evaluation as well as histopathological and electron microscopic examination of involved nerve segments showed significantly less epineurial adhesions in the DXR Group than in the Control Group. Quantitative analysis of the epineurium revealed a statistically significant reduction in the density and amount of epineural scarring in specimens from the DXR Group than in those from the Control Group. Conlusions The results of gross postsurgical anatomical evaluation and histopathological and ultrastructural studies suggested that topical application of DXR effectively reduced epineural scar formation on rat sciatic nerves. These promising findings merit further experimental and clinical studies to determine the efficacy and safe applicability of DXR in human subjects.


2019 ◽  
Vol 25 (3) ◽  
pp. 21-26
Author(s):  
Ye.V. Shaprynskyi

Scar strictures that lead to obstruction of the esophagus do not tend to decrease lately, but on the contrary, the number of such patients is increasing, which is caused by the use of a large range of chemicals in human life. The results of treatment of scarring strictures depend on the degree of stenosis. With complete obstruction of the esophagus, the question arises about conducting surgical treatment. Methods of correction of esophageal strictures have a considerable number of postoperative complications and lethal consequences – from 5.0 % to 15.0 %. Therefore, in order to create a unified pathogenetic tactic for the management and treatment of esophageal strictures, we were offered to study the ultrastructural changes of the mucous membrane of the stricture of the second stage during its modeling in the experiment. The purpose of the work is to investigate the dynamics of ultrastructural changes of the mucous membrane of the esophagus wall in the normal and second stage of its stricture. The experimental study was performed on adult white male rats weighing between 250 and 300 g. A total of 16 animals were operated on, which were divided into 2 groups: a control group (6 rats) and a study group (10 rats). The studies were performed under ketamine anesthesia. In animals of the control group performed only laparotomy, followed by layer-by-layer suturing of the anterior abdominal wall. In animals of the study group created a model of obstruction of the esophagus of the second stage. Electron microscopic examination was performed on days 3, 4, and 5 of the experiment, eliminating animals by overdosing on ketamine. As a result of the electron microscopic study of the ultrastructural organization of basal, spinosum, superficial epitheliocytes of stratified squamous epithelium without keratin, smooth muscle myocytes of the muscular plate and contractile elements of the muscular layer of the esophagus of rats with simulated stricture of the second degree revealed dystrophic and destructive disorders that varied in depth and severity. It was established that mitochondrial dysfunction leads to a decrease in the activity of reparative, metabolic and synthetic processes of the cell, which is indirectly manifested by a decrease in ribosomes and polysomes in the cytoplasm, loosening and focal lysis of membranes of the granular endoplasmic reticulum. Stricture of esophagus of the second stage causes activation of catabolic intracellular processes in all cells, which is morphologically confirmed by the appearance in the cytoplasm of secondary lysosomes and inclusions of lipids.


Author(s):  
Yu. V. Halahan ◽  
O. Ye. Маievskyi ◽  
Yu. Y. Guminskyi ◽  
A. P. Korol ◽  
S. V. Prokopenko

Disruption of the metabolism of the essential amino acid methionine causes the syndrome of hyperhomocysteinemia. This pathological condition is associated with the risk of developing a number of diseases, including chronic liver disease. The mechanisms of liver tissue damage in hyperhomocysteinemia remain poorly understood and require more detailed study. The aim of the study is to establish the features of submicroscopic changes in the liver structure of old rats with hyperhomocysteinemia. The experimental study was performed on 22 white nonlinear old (24-26 months) male rats, which were divided into a control group and an experimental group. A model of persistent hyperhomocysteinemia was created by administering to rats of experimental group of thiolactone homocysteine at a dose of 200 mg/kg body weight intragastrically for 60 days. The study of ultrastructural changes in the lungs of rats was performed using an electron microscope PEM-125K. At experimental hyperhomocysteinemia in a liver of old rats there are changes in all structural components. Mitochondrial destruction and edema were observed in the vascular endothelium. Organelles have an enlightened matrix, a reduced number of cristae. A significant content of destructively altered mitochondria in endothelial cells indicates a failure of adaptation mechanisms. Erythrocyte sludges are observed in the lumens of the sinusoids. The number of fat-accumulating cells decreases, which indicates their transformation into fibroblasts and leads to the growth of collagen fibers, expansion of the sinusoidal spaces and the development of stromal fibrosis.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23160-e23160
Author(s):  
Polina S. Kachesova ◽  
Irina A. Goroshinskaya ◽  
Vladimir B. Borodulin ◽  
Ludmila A. Nemashkalova ◽  
Anastasiya V. Chudilova ◽  
...  

e23160 Background: It has been shown that metal nanoparticles (NPs) can inhibit a tumor growth. Oxidative processes play important roles in tumor development and growth. The aim of this study was to determine parameters of oxidative stress in the blood of tumor-bearing animals depending on the antitumor effect of iron NPs (30-50 nm). Methods: Male rats with transplantable lymphosarcoma (LS) in the main group (n = 21) were treated with eight i.p. injections of iron NPs (total doses of 10 mg/kg bw), the control LS rats (n = 20) received saline i.p. The activity of catalase, superoxide dismutase (SOD), content of glutathione (GSH) and malondialdehyde (MDA) in the red blood cells (RBC) and ceruloplasmin oxidase activity (CP) and MDA content in blood plasma were measured. These parameters were analyzed in rats with complete tumor regression (n = 12) after NPs treated and in cases of tumor growth (n = 9). Results: In RBC of control group the level of GSH and catalase activity were increased compared to healthy rats by 24% and 14.3% (p < 0.05), respectively. In spite of activation of the given antioxidant system components, the MDA content in RBC was increased by 45% (p < 0.01) compared to normal values. In plasma of control group we observed an increase in MDA by 167.4% (p < 0.01) and a decrease in CP by 36.8% (p < 0.001). In the main group there was a decrease in blood MDA level and the antioxidant system reorganization. The degree of changes depended on the antitumor effect of NPs: rats with tumor growth showed a tendency to the decreasing MDA in RBC and normalization of plasma MDA; MDA in rats with LS regression was similar to normal values. In the main group the CP activity did not differ from the values in healthy rats. GSH increased in animals with tumor growth by 218.6% and in the animals with the effect - by 69% compared to normal values (p < 0.01). SOD activity in the rats with LS growth increased by 42% and in the rats with LS regression it decreased by 30% (p < 0.01). Conclusions: The data suggest the relationship between antitumor effect and modulating action on oxidative processes in LS rats treated by iron NPs. Iron NPs improved efficiency of antioxidant system in blood and contributed to suppression of oxidative stress associated with tumor growth.


2020 ◽  
Vol 36 (2) ◽  
pp. 84-92
Author(s):  
Ayşe Başardı Gökçe ◽  
Banu Eren ◽  
Dilek Sağir ◽  
Burcu Demirel Yilmaz

In this study, the effects of a potent antioxidant, selenium, on apoptosis induced by acrolein, a cytotoxic and genotoxic environmental pollutant, were investigated by immunohistochemical and electron microscopic methods. One hundred adult male Wistar albino rats were used in the study. The rats were divided into four main groups: control, acrolein, selenium, and acrolein + selenium. The animals in the experimental groups were given 1 mg/kg/day selenium and 4 mg/kg/day acrolein daily for 7 days by gavage. After drug administration, each group was divided into subgroups according to the time they were to be euthanized: 12th hour, 1st, 2nd, 3rd, and 5th day. The rats in each group at the determined time were euthanized and their livers were removed. Routine histological procedures were performed for light and electron microscopy examinations. After applying the Terminal Deoxynucleotidyl Transferase dUTP nick end labeling assay on the liver sections, apoptotic index values were calculated. Comparing the liver sections of the rats in the acrolein group and the control group, acrolein was found to cause a significant increase in the apoptotic index. The apoptotic index values of the acrolein + selenium group decreased compared to the acrolein group. In the electron microscopic examinations, apoptotic findings were observed in the liver tissues of the rats given acrolein, such as chromatin condensation in the nucleus of hepatocytes, dilatations in the perinuclear space, and cytoplasmic vacuolization. These apoptotic findings were not observed in the acrolein + selenium group after the 12th hour. These findings show that selenium may potentially be useful as a protective agent for people exposed to acrolein.


2021 ◽  
Vol 29 (3) ◽  
pp. 326-333
Author(s):  
S.V. Volkov ◽  
◽  
S.L. Lobanov ◽  
B.S. Erdineyeva ◽  
A.A. Dutova ◽  
...  

Objective. To determine the composition of the the parietal microflora of the colon under the condition of a tumor process and to assess the possibility of using these data from this study in the diagnosis of the colon cancer. Methods. The main group included patients (n=75) operated on in the Trans-Baikal Regional Oncology Center for the colon cancer. Among them are 38 men and 37 women aged 20 to 75 years. Control group consisted of 25 patients. The material of the main group, biopsies of tumor tissue and visually unchanged colon mucosa was taken intraoperatively during tumor removal. In patients of the control group, the material was taken during the colonoscopy. process. The detection of Helicobacter pylori in the biopsy of the mucous membrane was carried out by determining the urease activity, as well as by the method of polymerase chain reaction. The composition of the intestinal microbiota was determined by the bacteriological method. Results. As a result of comparison of the colon microbiota of the cancer patients and the control group, statistically significant differences in the quantitative composition of Lactobacillus spp., Bifidobacterium spp., Bacteroides spp., Clostridium spp., Enterococcus spp., E. coli (typical), E. coli (lactose-negative), Enterobacteriaceae, Staphylococcus spp. (CNS), Candida spp. were revealed. Moreover, a clear tendency of changes in the level of certain microorganisms (Bifidobacterium spp., E. coli (typical), Clostridium sp.) was detected when comparing the mucous membrane of a healthy person, unchanged mucous membrane of a patient with colorectal cancer, tumor tissue. A statistically significant dependence of the level of microorganisms on the sex of a patient, as well as the form of tumor growth, was revealed. Conclusion. Thus, a reliable correlation between the clinical and morphological characterization of the colon malignant tumor and the composition of the intestinal microbiota has been revealed. The microbiological features established within in the course of the study, which arise precisely under the conditions of colon cancer, can be used as an additional diagnostic marker in the diagnosis of a malignant process. What this paper adds It was found that thequantitative composition of the intestinal microbiota during the transformation into mucous and malignant tumor tissue in colon cancer and the correlation of specific microorganisms with the patient’s gender and the form of tumor growth. The state of the intestinal microbiota may represent a promising diagnostic marker for the detection of a malignant tumor.


2006 ◽  
Vol 22 (9) ◽  
pp. 395-398 ◽  
Author(s):  
Engin Deveci

Maneb is a dithiocarbamate fungicide that contains manganese. Dithiocarbamates are considered to be chemicals of low toxicity. An experimental group (n=10) received maneb (obtained from Hoecht-Shering) at a concentration of 250 ppm in distilled water five days a week (treatment time is three weeks). It was orally administered by an orogastric tube. Acute oral LD 50 for male rats has been found to be 6750 mg/kg. The control group (n=10) received distilled water. The whole body and testis weights of male rats were taken, and significant differences in body weight appeared between the control and treated groups (P<0.01). No statistical difference was found in the testis weights between the control and treated groups (P<0.05). Degeneration in spermatic cells can be seen in a few seminiferous tubules and vascularization. Transmission electron microscopy, interstitial cell and blood vessels of maneb-treated rat testis did not show any changes. Leydig cells with their large, excentric nuclei, cytoplasm with granular endoplasmic reticulum and other cell organelles appeared to be normal. Sertoli cells appeared unusually as a well developed rough endoplasmic reticulum and Golgi complexes had irregular compacted chromatin. Changes in Sertoli cell mitochondria included swelling and loss of cristae. Toxicology and Industrial Health 2006; 22: 395-398.


Author(s):  
Yu. V. Halahan ◽  
O. Ye. Maievskyi ◽  
Yu. Yo. Guminskyi ◽  
A. P. Korol

One of the important tasks of modern science is to find biochemical markers that would be able to reflect the risks of development and the nature of the course of various diseases, as well as to predict their possible consequences. In recent years, a significant number of compounds that can affect the biochemical profile of the organism have been identified. Homocysteine – a product of methionine metabolism, belongs to one of these markers, and the effects of its influece on the structure and function of various organs are being actively studied by modern researchers. The aim of the study is to find the patterns of electron microscopic changes in the liver structure of adult rats with hyperhomocysteinemia. The experimental study was performed on 22 white nonlinear mature male rats, which were divided into a control group and an experimental group. A model of persistent hyperhomocysteinemia was created by administering to rats of experimental group thiolactone homocysteine at a dose of 200 mg/kg body weight intragastrically for 60 days. The study of ultrastructural changes in the liver of rats was performed using an electron microscope PEM-125K. In adult rats with experimental hyperhomocysteinemia at the ultrastructural level, dystrophic and destructive changes in hepatocytes, endotheliocytes in the walls of sinusoids and Kupffer cells were found. These changes were more pronounced than in young rats with experimental hyperhomocysteinemia. Revealed structural changes in decompensation (depletion) of mitochondria – fewer number of cristae and enlightened matrix. In contrast to young rats, adult rats with hyperhomocysteinemia in the perisinusoidal spaces showed elongated Ito cells, a significant proportion of the cytoplasm is occupied by the Golgi complex and granular endoplasmic reticulum tanks, indicating protein synthesis for export. In Ito cells, the content of fat droplets, which are located on opposite poles of cells, is reduced. This morphological picture manifests the transformation of Ito cells into fibroblasts.


2015 ◽  
Vol 96 (4) ◽  
pp. 518-522
Author(s):  
O B Abdurakhmanov

Aim. To determine the association between morphological characteristics of tumor growth and clinical manifestations of progression. Methods. The study included 118 patients with juvenile nasopharyngeal angiofibroma who were examined and treated at the department of head and neck cancer of Cancer Research Center of Uzbekistan from 2003 to 2013. The main group included 69 patients with primary nasopharyngeal angiofibroma, control group - 49 patients with relapsing tumors who underwent surgery. Standard histological examination was performed in all patients. The algorithm for determination of morphological changes degree was developed based on approach proposed by K.M. Mardaleyshvili (1985), which was modified by authors. Results. Seven most important morphological features of juvenile nasopharyngeal angiofibroma were outlined. On this basis, we proposed to determine the degree of morphological changes for the prediction and treatment monitoring, which is a graded scale for the signs in each of the seven groups. In the main group of patients with cell type of juvenile nasopharyngeal angiofibroma growth, the scores ranged from 10 to 13, marking the 1st degree of morphological changes. Patients with vascular fibrous type of tumor growth had 18-19 points, which corresponds to the 2nd degree of morphological changes in the tumor. Tumor samples of patients with vascular fibrous type of juvenile nasopharyngeal angiofibroma had the most evident morphological changes in the tumor tissue, which corresponded to 3rd degrees with the scores reaching 28. Conclusion. The proposed algorithm for determining the grade of morphological characteristics may be used for determining the treatment tactics and monitoring the tumor growth in patients with juvenile nasopharyngeal angiofibroma, as well as the prognostic factor.


2019 ◽  
Vol 10 (2) ◽  
pp. 14-20
Author(s):  
E. A. Samishina ◽  
M. O. Dudina ◽  
E. V. Blinova ◽  
I. R. Suslova ◽  
O. N. Deryabina ◽  
...  

Aim. To study antitumor and anti - metastatic action of AKh-554, 2-Aminium-7-(Diethylamino)-4-(4-Metoxibenzo[d][1,3]dioxol-5-yl)-4H-chromene-3-carbonytril N-Acetylamino - ethanoate, on in vivo model of lung adenocarcinoma patient - derived xenograft model. Materials and methods. In 40 immunodeficient nu/nu BALB/c female mice with heterotopic patient - derived lung adenocarcinoma xenograft model antitumor and anti - metastatic effects of 2-aminochromene derivative, AKh-554 at dose 50 mg/kg intragastrically during 7 days, were explored. Laboratory animals were randomly designated into four groups - intact mice, control, referent drug and main group. We used Cyclophosphamide as referent drug. In the tumor tissue of the animals treated with the derivative through intragastric rout we quantitively detected TUBB3, ALK and c-MET/HFG levels.Results. AKh-554 more than 7.5 times decreases both the growth rate and size of xenograft tumor when compared with control group ( p =0.001), and possesses an anti - metastatic effect. Experimental treatment up to 103±2 days increases the lifespan of tumor carriers ( p =0.001 when compared with the control; p =0.03 when compared with cyclophosphamide), and induces remission in 60% of all cases. The established effect is due to activation of tumor cells apoptosis associated with decrease in tumor tissue ALK concentration (2.77±0.54 ng/ml; p =0.001 when compared with the control and cyclophosphamide). Experimental models demonstrate no signs of pharmacological resistance to AX-554, which is confirmed by the absence of differences of c-MET/HFG tissue level in all the studied groups (0.16±0.07 ng/ml - control; 0.09±0.03 ng/ml - Cyclophosphamide; 0.10±0.04 ng/ml - AKh-554).Conclusions. AKh-554 more effectively than Cyclophosphamide inhibits xenograft tumor growth and its metastatic activity. The compound increases more than 3.3 times when compared with the control the lifespan of experimental animals and induces remission of the malignant process in 60% of tumor carriers. The compound anticancer property is due to anti-ALK-mediated activation of tumor cells’ apoptosis and suppression of cell proliferation processes.


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