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Wohlfart S.,Goethe University Frankfurt | Khalansky A.S.,Institute of Human Morphology | Gelperina S.,Nanosystem Ltd. | Maksimenko O.,Nanosystem Ltd. | And 3 more authors.
PLoS ONE | Year: 2011

Background: Chemotherapy of glioblastoma is largely ineffective as the blood-brain barrier (BBB) prevents entry of most anticancer agents into the brain. For an efficient treatment of glioblastomas it is necessary to deliver anti-cancer drugs across the intact BBB. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with poloxamer 188 hold great promise as drug carriers for brain delivery after their intravenous injection. In the present study the anti-tumour efficacy of the surfactant-coated doxorubicin-loaded PLGA nanoparticles against rat glioblastoma 101/8 was investigated using histological and immunohistochemical methods. Methodology: The particles were prepared by a high-pressure solvent evaporation technique using 1% polyvinylalcohol (PLGA/PVA) or human serum albumin (PLGA/HSA) as stabilizers. Additionally, lecithin-containing PLGA/HSA particles (Dox-Lecithin-PLGA/HSA) were prepared. For evaluation of the antitumour efficacy the glioblastoma-bearing rats were treated intravenously with the doxorubicin-loaded nanoparticles coated with poloxamer 188 using the following treatment regimen: 3×2.5 mg/kg on day 2, 5 and 8 after tumour implantation; doxorubicin and poloxamer 188 solutions were used as controls. On day 18, the rats were sacrificed and the antitumour effect was determined by measurement of tumour size, necrotic areas, proliferation index, and expression of GFAP and VEGF as well as Isolectin B4, a marker for the vessel density. Conclusion: The results reveal a considerable anti-tumour effect of the doxorubicin-loaded nanoparticles. The overall best results were observed for Dox-Lecithin-PLGA/HSA. These data demonstrate that the poloxamer 188-coated PLGA nanoparticles enable delivery of doxorubicin across the blood-brain barrier in the therapeutically effective concentrations. © 2011 Wohlfart et al. Source

Postovalova E.A.,Moscow State University | Khochansky D.N.,Institute of Human Morphology | Zolotova N.A.,Moscow State University | Gao Y.,Moscow State University | And 2 more authors.
Bulletin of Experimental Biology and Medicine | Year: 2016

Morphological changes in the mesenteric lymph nodes of male C57Bl/6 mice and subpopulation composition of lymphocytes in these nodes were studied in experimental acute and chronic ulcerative colitis induced by sodium dextran sulfate. Acute and chronic ulcerative colitis was associated with the development of reactive changes in the mesenteric lymph nodes. These changes were of mixed type and were characterized by follicular hyperplasia and sinus reaction. The content of CD19+ B cells in the mesenteric lymph nodes decreased in acute ulcerative colitis, while the content of CD3+CD8+ cytotoxic T cells increased, which presumably reflected activation of Th1 reactions. The increase in the count of CD4+CD25+FOXP3+ regulatory T cells and CD3+CD8+ cytotoxic T cells was due to intensive migration of lymphocytes from the thymus and the colonic compartment of the local immune system. Chronic ulcerative colitis was associated with higher levels of CD19+ B cells and CD3+CD4+ T helper cells in the mesenteric lymph nodes, which was characteristic of adoptive immunity reactions and chronization of the inflammatory process. © 2016 Springer Science+Business Media New York Source

Yaglova N.V.,Institute of Human Morphology | Yaglov V.V.,Institute of Human Morphology
Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry | Year: 2015

Endocrine disruptors are exogenous substances that enter the body and exhibit hormone-like action thus disrupting the homeostatic action of endogenous hormones. The most wide-spread disruptor is dichlorodiphenyltrichloroethane (DDT). The aim of this study was to investigate changes in thyroid hormone production induced by prolonged exposure to low doses of DDT. The experiment was performed on male Wistar rats treated with daily doses of DDT 1.89 ± 0.86 μg/kg and 7.77 ± 0.17 μg/kg for six and ten weeks. After six weeks there was a dose dependent increase of serum total thyroxine, total triiodthyronine, and thyroid peroxidase. Subsequently, concentration of free thyroxine decreased. These data indicate that impaired production of thyroxine by follicular thyrocytes, rather than decreased deiodinase activity and blood transport proteins is the major cause of altered thyroid status induced by DDT. © 2015, Pleiades Publishing, Ltd. Source

Khalansky A.S.,Institute of Human Morphology | Hekmatara T.,Goethe University Frankfurt | Bernreuther C.,University of Hamburg | Rubtsov B.V.,Institute of Human Morphology | And 6 more authors.
Russian Journal of Biopharmaceuticals | Year: 2011

As shown previously, doxorubicin bound to the biodegradable poly(butyl cyanoacrylate) nanoparticles coated with polysorbate 80 (Dox-NP) significantly enhanced survival in the orthotopic rat 101/8 glioblastoma model; long-term remission was achieved in 20 - 40 % animals. This tumour has been shown to be an adequate model for experimental chemotherapy, its morphological features of the 101/8 glioblastoma (infiltrative growth pattern, high proliferation rate, vascularization, and pronounced necrotization) being similar to human glioblastomas. The objective of the present study was to investigate the morphological parameters of the antitumour effect of the Dox-NP. The tumor-bearing animals were subjected to chemotherapy using doxorubicin in solution (Dox) or Dox-NP injected intravenously on days 2, 5 and 8 post tumor implantation. The antitumor effect was assessed on days 10, 14 and 18 post tumor implantation. Tumors showed signs of malignancy including invasion of brain tissue, brisk mitotic activity, microvascular proliferation, necrosis and increased proliferation resembling human glioblastoma. Dox-NP produced a considerably more pronounced antitumor effect exhibited as a reduced tumor size, lower proliferation, and a decreased necrotic area compared to Dox and to untreated control groups. A drastic effect of Dox-NP on vascularization indicated an antiangiogenic mode of action. Source

El'chaninov A.V.,Moscow State University | Fatkhudinov T.K.,Moscow State University | Kananykhina E.Y.,Institute of Human Morphology | Usman N.Y.,Institute of Human Morphology | And 4 more authors.
Bulletin of Experimental Biology and Medicine | Year: 2016

In the liver of rats subjected to subtotal liver resection (80% organ weight), the expression of sox9 gene and SOX9 protein content increased and cells with hepatocyte morphology expressing SOX9 appeared; the proportion of cells expressing cytokeratin-19 also increased. Based on these data, we cannot completely exclude the involvement of resident progenitor cells and hepatocyte reprogramming in liver regeneration after subtotal resection, however, the contribution of these processes seems to be insignificant. The leading mechanism of liver mass recovery after subtotal resection is proliferation of hepatocytes. © 2016, Springer Science+Business Media New York. Source

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