Remodeling of the Extracellular Matrix of the Liver in Mice with BCG-Induced Granulomatosis after Administration of Liposome-Encapsulated Composition of Oxidized Dextran and Isonicotinic Acid Hydrazide

Bulletin of Experimental Biology and Medicine - Remodeling of the extracellular matrix of the liver in mice with BCG-induced granulomatosis after 2-month course of intraperitoneal injections of...     

Effect of Liposome-Encapsulated Dextrazide on Local Regulation of Extracellular Matrix Metabolism in Liver and Lungs of Mice with during Chronic BCG-Induced Granulomatosis

Bulletin of Experimental Biology and Medicine - The liposomal form of isonicotinic acid hydrazide conjugate with oxidized dextran (liposomeencapsulated dextrazide, LEDZ) injected intraperitoneally...     

Effects of Molecular Liposomal Hybrid Compositions with Oxidized Dextrans and Isonicotinic Acid Hydrazide on Production of Granulocytic Macrophage Colony-Stimulating Factor by Macrophages

The effects of molecular liposomal hybrid compositions consisting of liposomes (200–450 nm) containing oxidized dextrans (dextranals; 35–60 kDa) conjugated with isonicotinic acid hydrazide (dextrazides), their components, and native dextrans on the production of granulocytic macrophage CSF by peritoneal macrophages were studied in vitro. Dextranals proved to be more potent inductors of granulocytic macrophage CSF than native dextrans. Conjugation of nicotinic acid hydrazide with dextranals did not modify their capacity to stimulate the production of granulocytic macrophage CSF. Liposomes in the molecular liposomal hybrid compositions did not attenuate the dextrazide capacity to stimulate the production of granulocytic macrophage CSF. Molecular liposomal compositions containing 60 kDa dextrazide exhibited the most potent stimulatory effect on macrophage production of granulocytic macrophage CSF.     

Phagocytosis of Hybrid Molecular Nanosomal Compositions Containing Oxidized Dextrans Conjugated with Isonicotinic Acid Hydrazide by Macrophages

We studied phagocytic activity of macrophages towards hybrid molecular nanosomal compositions consisting of 150-800-nm nanoliposomes containing oxidized dextrans with a molecular weight of 35 and 60 kDa obtained by chemical (“permanganate”) and radiochemical oxidation of dextran conjugated with isonicotinic acid hydrazide (dextrazides, intracellular prolonged antituberculous drugs). Phagocytic activity of macrophages towards hybrid molecular nanosomal compositions containing dextrazides obtained by chemical oxidation of dextrans is higher than activity towards hybrid molecular nanosomal compositions containing dextrazides prepared by radiochemical oxidation and depends on the size of hybrid molecular nanosomal compositions and molecular weight of oxidized dextrans.     

Correlations between the Levels of the Main Extracellular Matrix Components in Mouse Liver in Chronic BCG-Induced Granulomatosis

Bulletin of Experimental Biology and Medicine - Correlations between extracellular matrix components in mouse liver revealed the pathogenetically determined dynamic structure of these...     

Phagocytic Activity of Macrophages against Liposomes with Conjugates of Oxidized Dextrans and Isonicotinic Acid Hydrazide during Modeling of Phagocytosis Disturbances In Vitro

We studied phagocytic activity of macrophages against molecular-liposome hybrid compositions consisting of liposomes (diameter 200–450 nm) containing oxidized dextrans with a molecular weight of 35 or 60 kDa conjugated with the basic antituberculosis preparation isonicotinic acid hydrazide (dextrazides) during modeling of various disturbances of endocytosis function of phagocytic cells in vitro. Preincubation of macrophages with trypsin, colchicine, or sodium azide did not change the parameters of adhesion of molecular-liposome hybrid compositions to macrophages. It was found that preincubation of cells with colchicine or sodium azide reduced parameters of phagocytosis of the molecular-liposome hybrid compositions; this reduction did not depend on the molecular weight of dextrans entering the composition of the molecular-liposome hybrid compositions.     

Morphological Study of the Efficiency of Isoniazid and Dialdehyde Dextran Composition in the Treatment of Mice with BCG Granulomatosis

Male BALB/c mice were intraperitoneally injected with BCG vaccine. After 1 month therapy was started: isoniazid or composition of isoniazid with dialdehyde dextran (CID) obtained by chemical and radiochemical methods. The therapeutic efficiency evaluated by the number granulomas in the liver and lungs and granuloma size was higher in mice treated with CID obtained by the radiochemical method in comparison with mice treated with isoniazid and with CID obtained by the chemical method. Hepatotoxicity evaluated by volume density of degenerative hepatocytes and necrotic zones was higher in mice treated with CID obtained by the radiochemical method than in animals treated with isoniazid, because CID contained free isoniazid and isoniazid bound to dialdehyde dextran. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Suppl. 1, pp. 105–108, 2008     

Effect of Dialdehyde Dextran on Structural Changes in the Liver and Lungs during Chronic BCG Granulomatosis

Male BALB/c mice were intraperitoneally infected with BCG vaccine. Cytomorphological changes in BCG granulomas of the liver and lungs were compared during spontaneous tuberculous inflammation and after intraperitoneal injection of dialdehyde dextran for 5 months. Administration of dialdehyde dextran to mice infected with mycobacteria of BCG vaccine was followed by a decrease in the number and size of BCG granulomas in organs, contributed to the increase in the count of fibroblasts in hepatic and pulmonary granulomas, decreased the severity of destructive changes in the liver parenchyma, promoted reparative processes in hepatocytes, and reduced the degree of fibrosis in the liver and lungs due to a decrease in fibroplastic activity of fibroblasts in BCG granulomas. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Suppl. 1, pp. 113–115, 2008     

Structural Changes in the Liver Parenchyma and Granulomas of Mice with Chronic BCG Granulomatosis during Therapy with Composition of Isoniazid and Dialdehyde Dextran

Male BALB/c mice were intraperitoneally infected with BCG vaccine. The therapy with isoniazid or composition of isoniazid with dialdehyde dextran (intraperitoneally, twice a week for 5 months) was started 1 month after infection. The retention time of the isoniazid-dialdehyde dextran composition in hepatocytes was much longer compared to that of isoniazid. The mice receiving the composition of isoniazid and dialdehyde dextran were characterized by a more significant decrease in the number and size of BCG granulomas, lower severity of destructive changes in the liver parenchyma, and more pronounced reparative regeneration (compared to animals of the isoniazid group). Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Suppl. 1, pp. 116–119, 2008     

Expression of Matrix Metalloproteinases in Invasive Pulmonary Adenocarcinoma with Bronchioloalveolar Component and Atypical Adenomatous Hyperplasia

To investigate the association between the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) and the clinicopathological features in lepidic and invasive components of adenocarcinoma of the lung, we performed immunostaining for type IV collagen, various MMPs, and TIMPs in 27 cases of invasive adenocarcinomas and 5 cases of atypical adenomatous hyperplasia of alveolar epithelial cells (AAH). Mean extent of lepidic growth was 61% and the survival was significantly better in cases with 50% or more lepidic component. The preservation of type IV collagen in lepidic areas correlated inversely with lymphatic or vascular invasion (P = 0.02 and 0.002, respectively). Five-year survival was reduced in cases showing destruction of type IV collagen (P = 0.004) or expression of MMP-2 (P = 0.008) in lepidic areas. MMP-2 co-localized with MT-1-MMP (its activating enzyme) and TIMP-2 in neoplastic cells. Reactivity for other MMPs and TIMPs did not correlate with destruction of type IV collagen or prognosis. Type IV collagen was preserved in all cases of AAH. MMP-2, but not MT-1-MMP, was expressed in two of the five cases of AAH. Immunostaining for type IV collagen MMP-2 is useful in evaluating the prognosis of the lung.     

Effect of Boar Seminal Immunosuppressive Component on Humoral Immune Response in Mice

PROBLEM: The effect of seminal immunosuppressive component (ISF) on the primary and secondary antibody response, induced by soluble and/or corpuscular antigens, was evaluated in the sera obtained at different intervals before and after immunizations. The duration of the immune suppression induced by ISF treatment within the primary and secondary immunizations was also determined. METHOD OF STUDY: The ability of the seminal immunosuppressive component to suppress the primary and secondary antibody response was evaluated by enzyme-linked immunoadsorbent assay (ELISA) in the sera of mice treated in vivo with the immunosuppressor before and after immunization with antigens. Likewise, the duration of the immune suppression induced by the seminal immunosuppressor administered before the primary and secondary immunizations was tested by ELISA with antisera to keyhole limpets hemocyanin. RESULTS: Intravenous and rectal deposition of ISF led to a suppression of the primary and secondary antibody response to soluble and corpuscular antigens. The most effective suppression of the immune response was achieved in mice treated with immunosuppressor 3 days before the immunization with antigens. Also the secondary antibody response to the challenging antigen was significantly suppressed by ISF. The production of immunoglobulin G (IgG), IgM, and IgA to keyhole limpets hemocyanin was depressed for a relatively long period in mice treated with the immunosuppressor. The results indicated that the preexposure is needed for maximal immunosuppression of the primary antibody production. The treatment with ISF led to a prolonged immunosuppression but not to permanent tolerance to the challenging antigen. CONCLUSIONS: The in vivo deposition of semen may compromise some aspects of the immune system and may be an important factor in the development of viral and bacterial infections. The suppression of humoral immune response suggests potential uses of seminal immunosuppressor for the animal model study in the therapy of antibody-mediated diseases.     

Inhibitory Effect of Recombinant IL-25 on the Development of Dextran Sulfate Sodium-Induced Experimental Colitis in Mice

The role of interleukin 25 （IL-25） in a number of human diseases still has not been extensively studied, here we attempt to evaluate the role of recombinant IL-25 （rIL-25） in the development of dextran sulfate sodium （DSS）- induced experimental colitis. Acute colitis was induced in female C57BL/6 mice by oral administration of 2.5% DSS in drinking water ad libitum. At the same time as the start of DSS exposure, mice were injected intraperitoneally with 0.4 ＋tg of rIL-25 or PBS. Then disease activity index （DAI）, histological changes and survival rate were observed. The levels of IL-17, IL-23, and TGF-β1 in colon tissues were determined by ELISA, and the production of IL-17 by CD4＋/CD8＋ T cells was detected by intracellular flow cytometry. In contrast to the DSS treated mice, DSS ＋ rIL-25 treated mice displayed a lower DAI, limited histological changes and prolonged survival. The levels of IL-23 and TGF-β1 were significantly elevated in the DSS ＋ rIL-25 treated mice compared to the DSS treated mice. There was no significant difference in the production of IL-17 in colon tissues and CD4＋/CD8＋ T cells between the DSS ＋ rIL-25 treated mice and DSS treated mice. Our findings suggest the role of IL-25 in inhibiting development and progression of acute colitis in DSS-induced mouse colitis model. Cellular ＆ Molecular Immunology. 2008;5（6）：425-431.     

Effects of Dextran Sulfate 500 on Cell-Mediated Resistance to Infection with Listeria monocytogenes in Mice

Injection of dextran sulfate 500 caused loss of antibacterial resistance. Mice became more susceptible to an infection with Listeria monocytogenes and were unable to develop antilisterial immunity after both active and passive immunization with passively administered spleen cells from Listeria-immune donors. Indirect evidence suggests that the phagocytic component of cell-mediated resistance to bacterial infection is the site of attack of dextran sulfate.     

中和IL－17对博莱霉素诱导的肺纤维化小鼠肺组织Bax／Bcl－2表达的影响

目的：研究中和IL－17 A对博莱霉素（ bleomycin, BLM）诱导的肺纤维化小鼠肺组织Bax／Bcl－2表达的影响。方法将小鼠分别分成生理盐水组、 BLM组、 IL－17 A抗体组和IL－17 A抗体对照组,各30只,利用HE染色、 Masson三色胶原纤维染色检测小鼠肺组织纤维化程度,免疫组化方法检测小鼠肺组织Bax／Bcl－2的表达。结果从生理盐水组、到IL－17 A抗体组、再到BLM组和IL－17 A抗体对照组,小鼠肺组织肺泡炎症程度、肺泡壁的增厚情况以及肺泡壁的纤维化程度逐渐加重,差异有显著性意义（P＜0．01）; BLM组和IL－17 A抗体对照组间无明显差异（P＞0．05）。4组间Bax蛋白、 Bcl－2蛋白的表达也逐渐加重,差异均有统计学意义（ P＜0．01和P＜0．05）。 BLM组与抗体对照组间Bax、 Bcl－2的表达均无显著差异（P＞0．05）。结论 BLM可通过IL－17 A来诱导肺纤维化的形成,肺纤维化时肺实质细胞凋亡增多,而中和IL－17 A可通过调节Bax／Bcl－2的表达来抑制肺组织气道上皮的凋亡、达到抑制肺纤维化的目的。     

维甲酸治疗博莱霉素诱发大鼠肺间质纤维化

观察维甲酸（RA）的抗纤维化作用并初步探讨其作用机理。RA治疗博莱霉所致肺纤维化大鼠28天后,病理观察及形态定量分析示肺纤维化程度明显减轻,肺组织胶原蛋白含量较同期纤维化对照组（BLM组）减少（113．86±13．86mg/glung;152．40±11．00mg／glung,P＜0．01）。RA组支气管肺泡灌洗液中转化因子β1（TGF-β1）含量在第7、14天时则较同期BLM组显著下降（P均＜0.01）。RA治疗后,肺组织原胶原α1（Ⅰ）．（Ⅲ）及TGF-β1．mRNA水平也有明显的降低。RA能有效阻止实验性肺间质纤维化的发生和发展。RA抑制肺组织TGFβ1的表达是其抗纤维化作用的重要机制之一。     

生物陶瓷与细胞外基质对成骨细胞生长及代谢影响

本研究采用了体外细胞培养技术,将人胚成骨细胞分别与不同生物陶瓷(HA,TCP,FHA,BGC)及复合生物陶瓷(BMP,TGF-β1)共同培养.通过相差显微镜及扫描电镜观察材料表面及周围细胞形态及附着情况,分子生物学方法测定细胞增殖率,碱性磷酸酶(ALP)、骨钙素(OC)、白细胞介素6(IL-6)及转化生长因子β1(TGF-β1)分泌水平,探讨其作用机理.结果发现复合生物陶瓷细胞增殖率,ALP、OC、IL-6及TGF-β1水平明显高于相应单一材料及空白对照.而不同的复合材料细胞增殖率及细胞基质蛋白分泌有所差异.FHA BMP,TCP BMP及HA BGC TGF-β1显示了较高水平.不同材料培养不同时间对细胞生长及代谢影响有所不同,反映了成骨细胞培养方法评价人工骨替代材料成骨活性规律是切实可行的.     

Effect of Atorvastatin on Activities of Matrix Metalloproteinases and Chitotriosidase in Male and Female Mice with Experimental Hyperlipidemia

Activities of matrix metalloproteinases and chitotriosidase were measured in blood serum from male and female ICR mice with moderate hyperlipidemia receiving atorvastatin (75 mg/kg). Hyperlipidemia in male and female mice was characterized by increased serum concentration of cholesterol and, especially, triglycerides. The observed changes were more pronounced in female mice. Administration of atorvastatin decreased cholesterol (but not triglyceride) level in intact males, but had no effect on these parameters in females; chitotriosidase activity increased in male and female mice, while activity of matrix metalloproteinases increased only in males. Administration of atorvastatin produced similar effects in male and female mice with moderate hyperlipidemia: decrease in the concentration of cholesterol and, particularly, of triglycerides. Activities of matrix metalloproteinases and chitotriosidase increased in males and females, this increase being more pronounced in males. The existence of a negative correlation between cholesterol and triglyceride concentrations and activities of matrix metalloproteinases and chitotriosidase in males suggests that these enzymes can serve as a therapeutic target during hyperlipidemia.