A quantitative analysis of alterations in the shape of cultured fibroblasts induced by tumour-promoting phorbol ester

Quantitative analysis of cell size and shape has shown that the tumour promotor 12-o-tetradecanoylphorbol-13-acetate (TPA) alters one of three parameters of cell shape, dispersion. It has no effect on cell area or elongation. This reflects the fact that TPA causes cells to form long narrow processes extending from the cell body. The ability to measure alterations in specific parameters of cell shape is important for correlating changes in the observed behaviour of cells with effects on cytoskeletal organisation.     

Efficacy of cow's kumiss in the treatment of large intestine dysbacteriosis and its impact on tolerability of antituberculosis agents in patients with respiratory tract tuberculosis]

Dysbacteriosis of the large intestine is one of severe complications of long-term use of antituberculosis agents in the treatment of respiratory tract tuberculosis that results in a significant decrease of tolerability of antituberculosis agents, persistence of tuberculosis intoxication and slower involution of the tuberculosis process in the lungs. When the complex treatment with antituberculosis agents was accompanied by the use of cow's kumiss for correction of the large intestine dysbacteriosis, the intoxication signs disappeared in 12% of the patients in the main group, while in the patients of the control group the level of the intoxication syndrome increased twice. The rate of the tuberculosis lesions regression evident from the lung roentgenograms was 2.7-fold higher in the main group vs. the control (62 and 23% respectively). The indices of the lung functional capacity recovery in the patients of the main group vs. the control were also higher (41 and 33% respectively). Hepatic toxic reactions in the patients not given cow's kumiss for correction of dysbacteriosis were 8 times more frequent vs. the control. The results of the study made it possible to develop recommendations for phthisiologists in the use of cow's kumiss as one of the methods of pathogenetic therapy in complex treatment of patients with respiratory tract tuberculosis in sanatoria.     

Novel mitochondria-targeted compounds composed of natural constituents: Conjugates of plant alkaloids berberine and palmatine with plastoquinone

Novel mitochondria-targeted compounds composed entirely of natural constituents have been synthesized and tested in model lipid membranes, in isolated mitochondria, and in living human cells in culture. Berberine and palmatine, penetrating cations of plant origin, were conjugated by nonyloxycarbonylmethyl residue with the plant electron carrier and antioxidant plastoquinone. These conjugates (SkQBerb, SkQPalm) and their analogs lacking the plastoquinol moiety (C10Berb and C10Palm) penetrated across planar bilayer phospholipid membrane in their cationic forms and accumulated in isolated mitochondria or in mitochondria in living human cells in culture. Reduced forms of SkQBerb and SkQPalm inhibited lipid peroxidation in isolated mitochondria at nanomolar concentrations. In isolated mitochondria and in living cells, the berberine and palmatine moieties were not reduced, so antioxidant activity belonged exclusively to the plastoquinol moiety. In human fibroblasts, nanomolar SkQBerb and SkQPalm prevented fragmentation of mitochondria and apoptosis induced by exogenous hydrogen peroxide. At higher concentrations, conjugates of berberine and palmatine induced proton transport mediated by free fatty acids both in model and in mitochondrial membrane. In mitochondria this process was facilitated by the adenine nucleotide carrier. As an example of application of the novel mitochondria-targeted antioxidants SkQBerb and SkQPalm to studies of signal transduction, we discuss induction of cell cycle arrest, differentiation, and morphological normalization of some tumor cells. We suggest that production of oxygen radicals in mitochondria is necessary for growth factors-MAP-kinase signaling, which supports proliferation and transformed phenotype.     

Receptors of the PAR Family as a Link between Blood Coagulation and Inflammation

Blood coagulation plays a key role among numerous mediating systems that are activated in inflammation. Receptors of the PAR family serve as sensors of serine proteinases of the blood clotting system in the target cells involved in inflammation.Activation of PAR-1 by thrombin and of PAR-2 by factor Xa leads to a rapid expression and exposure on the membrane of endothelial cells of both adhesive proteins that mediate an acute inflammatory reaction and of the tissue factor that initiates the blood coagulation cascade. Certain other receptors (EPR-1, thrombomodulin, etc.), which can modulate responses of the cells activated by proteinases through PAR receptors, are also involved in the association of coagulation and inflammation together with the receptors of the PAR family. The presence of PAR receptors on mast cells is responsible for their reactivity to thrombin and factor Xa and defines their contribution to the association of inflammation and blood clotting processes.     

Novel mitochondria-targeted antioxidants, “Skulachev-Ion” derivatives, accelerate dermal wound healing in animals

It is shown that the novel mitochondria-targeted antioxidant SkQ1, (10-(6′-plastoquinonyl) decyltriphenylphosphonium) stimulates healing of full-thickness dermal wounds in mice and rats. Treatment with nanomolar doses of SkQ1 in various formulations accelerated wound cleaning and suppressed neutrophil infiltration at the early (7 h) steps of inflammatory phase. SkQ1 stimulated formation of granulation tissue and increased the content of myofibroblasts in the beginning of regenerative phase of wound healing. Later this effect caused accumulation of collagen fibers. Local treatment with SkQ1 stimulated re-epithelization of the wound. Lifelong treatment of mice with SkQ1 supplemented with drinking water strongly stimulated skin wounds healing in old (28 months) animals. In an in vitro model of wound in human cell cultures, SkQ1 stimulated movement of epitheliocytes and fibroblasts into the “wound”. Myofibroblast differentiation of subcutaneous fibroblasts was stimulated by SkQ1. It is suggested that SkQ1 stimulates wound healing by suppression of the negative effects of oxidative stress in the wound and also by induction of differentiation. Restoration of regenerative processes in old animals is consistent with the “rejuvenation” effects of SkQ1, which prevents some gerontological diseases.     

Aptamer DNA: A New Type of Thrombin Inhibitors

The formation of complexes between various thrombin preparations and 30-mer aptamer DNA was comparatively studied, and a correlation between the complex formation and the fibrinogen-hydrolyzing activity of thrombin was found. The aptamer DNA was shown to inhibit the formation of fibrin from fibrinogen.     

Mycotoxigenic infestation in samples of cereal straw from Bihar, India

A survey of different types of cereal straw samples viz. paddy, maize and wheat, from Bihar State, India, was conducted in order to examine the mould flora and mycotoxin contamination. Out of 170 samples examined for mould flora,Aspergillus flavus group of fungi had highest level of incidence followed byA niger. Isolates ofA flavus, A ochraceus, Fusarium verticillioides andPenicillium citrinum were screened for their mycotoxins producing abilities. Out of 75, 63 and 68 isolates ofA flavus group obtained from stored straw of paddy, maize and wheat samples, respectively, 27 (36%), 14 (22%) and 24 (35%) were found to be toxigenic which produced different combinations of aflatoxins in different concentrations. The percentage toxigenicity was comparatively lower in the isolates of other mycotoxigenic fungi from all types of samples. Out of 222 samples of straw analysed for natural occurrence of different mycotoxins, besides the aflatoxins present, zearalenone, ochratoxin A and citrinin were also recorded alone or as co-contaminants. A conducive climate together with the socioeconomic conditions of this region are important determinants for the high incidence of mycotoxins in cereal straw samples.     

Aptameric DNA--a new type of thrombin inhibitor

The formation of complexes between various thrombin preparations and a 30-mer aptamer DNA was comparatively studied, and a correlation between the complex formation and the fibrinogen-hydrolyzing activity of thrombin was found. The aptamer DNA was shown to inhibit the fibrin formation from fibrinogen.