Effect of sodium selenite and its combination with remantadine on the synthesis of virus-specific polypeptides in a cell culture infected with influenza A virus

The combined effects of sodium selenite and remantadine on synthesis of virus-specific polypeptides in influenza A virus-infected CEC cells are described. The pattern of selenium distribution in subcellular fractions and biomacromolecules of different organs of rats was established. Combined use of sodium selenite and remantadine actively inhibits synthesis of influenza A virus polypeptides which is of synergistic nature.     

Protective action of remantadine in experimental influenzal-staphylococcal infection

The effect of remantadine on the course of influenzal-staphylococcal infection was studied in white mice. When the drug was injected to the mice infected with remantadine-sensitive strain of influenza A virus and Staphylococcus the lethality decreased from 93.3% to 26.7%, the survival time increased from 3.8 to 10.1 days, the incidence of pneumonia decreased from 85.7% to 48.7%, the average intensity of pneumonia decreased from 66.4% to 9.9%, and virus titres in the lungs decreased by 3.5-4.0 lg EID50 (p less than 0.05). In the groups of mice infected with remantadine-resistant strain of influenza virus and Staphylococcus remantadine showed no significant effect on these parameters: the lethality decreased by 6.7% only, the average survival time increased only by 0.33 days, the incidence of pneumonia decreased by 9%, its intensity by 19.2%; influenza virus titres in the lung tissue did not change significantly.     

Synergic therapeutic action of aprotinin and remantadine in experimental influenzal infection

Chemotherapeutic treatment of influenza infection is possible with aprotinine, an inhibitor of proteinases blocking proteolytic shearing of virion hemagglutinin which is necessary for multicycle virus infection. The chemotherapeutic effect of antiinfluenza drug remantadine is due to inhibition of intracellular deproteinization of virions in the course of their penetration into cells. In mice infected with a highly lethal dose (about 400 MLD50/animal) of influenza A/Aichi/2/68 (H3N2) virus treatment with remantadine protected from death 12% of the animals, aprotinine 36%, and combined treatment with aprotinine and remantadine induced protection in 72%. The mice receiving combined treatment showed minimal pathological lesions in the lungs whereas control untreated animals had total hemorrhagic pneumonia. Thus, combined use of drugs blocking different stages of virus reproduction may have a synergetic therapeutic effect inducing a potentiating protective effect in the animals inoculated with a high dose of influenza virus.     

Rationale for the treatment of cancer with sodium selenite

Epidemiological studies conducted during several decades of the last century have demonstrated the importance of sufficient nutritional supply of selenium (Se) for human health. More importantly, low blood Se levels were found to be associated with an increased incidence and mortality from various types of cancers. Recently, attention of researchers was drawn to the relationship between free radical generation, known otherwise as oxidative stress, and carcinogenesis. It was therefore thought that antioxidants should be beneficial for prevention and inhibition of different malignancies. However, there appeared to be a paradox, because tumor growth is associated with tissue hypoxia that is accompanied by the formation of reductive rather than oxidative free radicals. Various organic and inorganic Se compounds, generally considered to be antioxidants, produced mixed results when tested in animal models and human subjects. Amongst them, sodium selenite has been shown to be the most effective in an in vitro and in vivo carcinogenesis studies. As recently demonstrated, selenite is not an antioxidant, but possesses oxidizing properties in the presence of specific substrates. Thus selenite is capable of oxidizing polythiols to corresponding disulfides, but does not react with monothiols. Such polythiols associated with cancer membrane-bound proteins appear under the reducing conditions of hypoxic tumor tissue. These thiol groups can, in turn, initiate a disulfide exchange reaction with plasma proteins, predominantly with fibrinogen, to form an insoluble and protease-resistant fibrin-like polymer. As the result, tumor cells become surrounded by a coat which masks specific tumor antigens thus allowing cancer cells to escape immune recognition and elimination by natural killer (NK) cells. Selenite by virtue of oxidizing cell membrane thiols, can prevent the formation of the coat and consequently makes cancer cells vulnerable to the immune surveillance and destruction. In addition, selenite may directly activate NK cells, as well as inhibit angiogenesis without undesirable decrease in the oxidative potential of cellular environment. It is, therefore, postulated that sodium selenite, in view of its relative low toxicity, might become a drug of choice for many types of cancer including leukemia.     

Antiviral action of dipyridamole and its derivatives against influenza virus A

Dipyridamole proved to be active against influenza viruses A/England 42/72, A/Bangkok 1/79 and A/fowl plague (FPV). The antiviral activities assayed by various methods varied from 90-99 per cent. No inhibition was found against influenza virus B/Leningrad 235/74 in vitro. Three dipyridamole derivatives were significantly active in tissue cultures against influenza virus A/England 42/72 and A/FPV. In white mice infected with influenza virus A/England 42/72 dipyridamole administered orally showed a protection rate of 62.5 per cent.     

Antiviral action of gliotoxin

Summary Antiviral activity of gliotoxin can be demonstrated at approximately one-tenth of the concentration which produces toxic effects in tissue culture cells and embryonated eggs.The inhibition of picornaviruses in tissue culture varies quantitatively according to the strain of virus. Inhibition of influenza and parainfluenza viruses is found in embryonated eggs and chorioallantoic membrane pieces. No activity was found against any of the myxoviruses tested in tissue culture or against viruses containing deoxyribonucleic acid.Gliotoxin acts on a stage in the intracellular synthesis of susceptible picornaviruses and results in inhibition of the production of virus specific proteins.The adsorption of gliotoxin by cellsin vitro is rapid. Subsequent washing of the cells with gliotoxin-free medium does not result in a reversal of inhibition of virus synthesis.A related compound, dethiogliotoxin, which does not contain the disulphide bridge present in gliotoxin appears to have no specific antiviral or antibiotic activity. It is suggested that the antiviral activity of gliotoxin is associated with the presence of the linked sulphur atoms in the molecule.     

Antiviral action of monoclonal antibodies

The antiviral effect of monoclonal antibodies MAK-14-7 possessing the neutralizing activity was studied on the model of Venezuelan equine encephalomyelitis virus in cell cultures and in experimentally infected laboratory animals. Mouse monoclonal antibodies exerted a marked specific antiviral effect in tissue culture and in white mice inhibiting virus reproduction by 1-3-5 log PFU/ml. The degree of inhibition of virus reproduction is inversely proportional to the multiplicity of infection. When used in combination with remantadine, ribavirin, interferon, and its inducer poly (I) X poly (C), the monoclonal antibodies MAK-14-7 exerted additive antiviral effect.     

亚硒酸钠对人白血病HL-60细胞作用机制的研究

目的和方法：实验观察亚硒酸钠对人急性髓性白血病细胞系ＨＬ－ ６０ 细胞生长增殖、诱导分化、细胞内自由基产生和清除系统以及胞内环核苷酸累积的影响,探索亚硒酸钠对人白血病ＨＬ－ ６０ 细胞作用机制。结果：８ ×１０６ｍｏｌＬ 或更高浓度的亚硒酸钠均可显著抑制ＨＬ－ ６０ 细胞的生长增殖,作用５ ｄ 可在一定程度上诱导ＨＬ－ ６０ 细胞向成熟粒细胞方向分化。８ ×１０６ ｍｏｌＬ 亚硒酸钠作用一段时间,可增强自由基清除系统酶活性,减低胞内自由基水平,降低细胞内ｃＧＭＰ 累积而对ｃＡＭＰ 累积无明显影响。结论：硒的抗白血病作用可能与亚硒酸钠的这些作用相关     

亚硒酸钠对子宫内膜癌细胞增殖能力的影响

目的: 研究亚硒酸钠(Na₂SeO₃)对子宫内膜癌细胞增殖能力的影响,并探讨其作用机制。方法: 用Na₂SeO₃作用于子宫内膜癌Ishikawa细胞和HEC-1A细胞,MTT法检测细胞增殖能力,流式细胞法测定Na₂SeO₃作用后细胞周期的变化及凋亡情况,Western blotting检测周期蛋白cyclin A的表达。结果: Na₂SeO₃对子宫内膜癌Ishikawa细胞和HEC-1A细胞的增殖均有抑制作用,抑制率在一定浓度范围内与Na₂SeO₃浓度呈正相关,对Ishikawa细胞作用48 h的IC₅₀为3.26 μmol/L,对HEC-1A细胞作用48 h的IC₅₀为4.77 μmol/L。Na₂SeO₃作用后两种细胞G₀/G₁期减少,S期细胞增多,G₂/M期细胞有所增加。作用48 h后两种细胞凋亡率增加。Na₂SeO₃使子宫内膜癌Ishikawa细胞和HEC-1A细胞的cyclin A表达增加。结论: 亚硒酸钠对子宫内膜癌Ishikawa细胞和HEC-1A细胞增殖有抑制作用,其作用机制与上调cyclin A表达,引起细胞周期阻滞和诱导凋亡有关。     

亚硒酸钠对实验性自身免疫性甲状腺炎大鼠甲状腺细胞凋亡的影响

目的 探讨亚硒酸钠对实验性自身免疫性甲状腺炎(EAT)大鼠甲状腺细胞凋亡的影响.方法 Wistar大鼠分为正常对照组、自身免疫性甲状腺炎(EAT)组和硒干预EAT组.制备EAT大鼠模型,硒干预EAT组给予亚硒酸钠灌胃.用放射免疫法(RIA)测定各组大鼠自身抗体水平,HE染色观察甲状腺组织病理改变及TUNEL法标记甲状腺组织中凋亡细胞,观察甲状腺细胞凋亡情况.结果 正常对照组、EAT组、硒干预EAT组的TgAb分别(6.94±1.13)%、(36.24±3.64)%、(17.23±2.90)%,TmAb分别为(5.96±1.40)%、(27.12±5.06)%、(15.98±2.45)%.硒干预EAT组TgAb、TmAb水平较EAT组明显下降(P<0.05).各组大鼠甲状腺组织炎症程度及凋亡程度评分结果比较显示,不同组别的甲状腺组织病变程度间差别有显著性(P<0.001),硒干预EAT组的甲状腺滤泡破坏程度较EAT组减轻,淋巴细胞浸润减少(P<0.05),甲状腺细胞的凋亡数量较EAT组明显减少(P<0.05).结论 亚硒酸钠可能通过抑制甲状腺细胞的凋亡来减轻或抑制自身免疫性甲状腺炎的免疫损伤.     

亚硒酸钠对UVB损伤人角质形成细胞的保护作用

目的:研究亚硒酸钠(Na2Se O3)对中波紫外线(UVB)损伤人角质形成细胞的保护作用。方法:培养永生化人角质形成细胞(Ha Ca T细胞),实验分为4组处理:(1)正常对照组;(2)Na2Se O3组:分别加入1 nmol/L、10 nmol/L、50 nmol/L、100 nmol/L、200 nmol/L和1μmol/L的Na2Se O3预孵育24 h;(3)UVB组:300、600和900 J/m2UVB照射;(4)Na2Se O3+UVB组:Na2Se O3预孵育24 h后进行UVB照射。采用MTT法检测细胞增殖活性,采用流式细胞仪检测300 J/m2UVB照射后细胞的凋亡率。结果:(1)UVB组与正常对照组比较,细胞增殖活性显著降低(P0.05),细胞活性与UVB照射剂量呈负相关;(2)Na2Se O3组与正常对照组比较,细胞增殖活性无明显差异;(3)不同浓度Na2Se O3+UVB组与UVB组比较,细胞增殖活性增加,差异显著(P0.05),其中100 nmol/L组促进细胞增殖作用最强;(4)300 J/m2UVB照射后,不同浓度Na2Se O3+UVB组与UVB组比较,凋亡率下降,差异显著(P0.05),其中100 nmol/L组抑制凋亡作用最强。结论:UVB对角质形成细胞有损伤作用,且与照射剂量呈正相关;Na2Se O3具有光保护性能,可减轻UVB辐射损伤人角质形成细胞。