Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon

We have examined whether dietary polyamines influence the formation and initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rat colon. Effects of a combination of dietary polyamines at three dose levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g; spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied in animals in two different experimental situations: animals treated with AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a specific inhibitor of endogenous polyamine synthesis. In both experimental situations, dietary polyamines enhanced the growth of ACF, expressed as the number of large ACF (foci with three or more aberrant crypts, ACF > or = 3), whereas the formation of ACF, expressed as the number of ACF, was apparently not altered. In animals treated with AOM alone, maximal growth enhancing effect on ACF was nearly obtained with the median level of dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of DFMO was counteracted by dietary polyamines in a dose- dependent manner, and it was abolished at the highest level of polyamines. In conclusion, it was demonstrated that dietary polyamines are able to enhance the growth of AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused inhibition of ACF growth, probably by compensating for the DFMO-reduced endogenous polyamine synthesis.      

КoMплeкcooбpaзoBaN;иe гeпapиN;a c фибpиN;ct;aбилизиpyющиM фaкt;opoM in vitroThe formation of complex fibrin stabilizing factor with heparin in vitro

It has been found that heparin (Hp) forms a complex with fibrin stabilizing factor (FSF) in vitro. The formation of complex FSF-Hp has been testified by electrophoresis, analytical ultracentrifugation, spectral analysis in the regions of ultra-violet and ultra-red absorption and by study of differential spectrum of complex FSF-Hp.Maximum of specific biochemical activity of the complex FSF-Hp was estabilished when the weight relation between Hp and FSF reached 1:4, at pH 7,3. Complex FSF-Hp diminished specific activity when its formation was carried out in the conditions of raising or reducing weight ratio of Hp. The activity totally disappeared when ratio Hp:FSF was reached 1:1 or 1:15. Complex FSF-Hp obtained in optimal conditions acted as an inhibitor of polymerization (aggregation) of fibrin monomer. It also carried out the lysis of non-stabilized fibrin in the presence or absence of E-aminocaproic acid.The mentioned biochemical activity of complex FSF-Hp is very similar to one of complex fibrinogen-heparin, formation of which in vitro and in vivo and physiological significance we investigated before (2,3)     

Lysis of fresh experimental thrombi under the action of a secondary adrenaline-heparin-fibrinogen complex

It is shown that the epinephrine-heparin-fibrinogen complex, as well as a number of other complex compounds of heparin accomplish the prophylaxis of thrombogenesis at the initial stages of the process, the epinephrine-heparin-fibrinogen complex lysing the thrombi in an average of 48 minutes, while the complexes of fibrinogen-heparin and epinephrine-heparin do this in 2--4 hours. The complex heparin compounds exercise a thrombolytic action only on non-stabilized fresh thrombi with less than 15 minutes from the time of their formation.     

C-peptide, diabetogenic factor and the blood anticoagulating system in patients with the insulin-dependent type of diabetes mellitus before and after heparin therapy

The authors analyzed the results of investigation of insulin residual secretion determined by the concentration of C-peptide in response to the stimulation of 1 mg of glucagon. The blood level of the diabetogenic factor (DGF) and activity of the anticoagulative system (ACS) were studied in parallel in patients with insulin-dependent type of diabetes mellitus before and after heparin therapy. The blood DGF disappeared, ACS function was restored, and the patient's body resistance to blood hypercoagulation developed against a background of heparin therapy. A decrease in insulin residual secretion was shown to be related to a duration of diabetes mellitus.     

Physicochemical properties of the diabetogenic factor and its complex with heparin

The diabetogenic factor (DGF) isolated from the human blood and the blood of rats with diabetes mellitus was shown to be a protein homogeneous at electrophoresis in gel of polyacrylamide, with the molecular weight of 60,000 D. The interaction of DGF with heparin results in the formation of a complex in which the factor's properties are blocked and those of heparin as a anticoagulant are preserved.     

Знaчeниe AКTГ для пroцecca oбraзoвaния кomплeкcныч coeдинeний гeпarинa в кroви пrи иmmoбилизaциoннom cтrecceThe role of ACTH in the formation of heparin complexes in blood under immobilization stress conditions

Under stress condition due to 30 min immobilization the total non-enzymatic fibrinolytic activity in rats is increased 4-fold, its proportion in the overall fibrinolytic activity of blood plasma being increased 1,5-fold. After pretreatment with ACTH (5–15 units) the same stress leads to more significant increase of non-enzymatic fibrinolysis which is 2,5 times higher than that in the absence of ACTH. The activity of fibrinogenheparin, epinephrineheparin, plasminogenheparin and plasminheparin complexes is increased 1,5–2,5 fold. ACTH induced a more efficient formation of heparin complexes also in the absence of stress. Its action is revealed in the course of 24 hours. Under blocked ACTH secretion as a result of DOCA treatment immobilization stress does not followed by increase of complex formation. The effect of ACTH on the formation of heparin complexes is mediated by stimulation of the adrenal cortex and by an increase in the corticosteroid level in the organism. Evidence of this has been produced from experiments on rats using ACTH treatment at different intervals after adrenalectomy. During first 24 hours after adrenalectomy when the additional cortical tissue is yet not active the injection of ACTH does not intensify heparin complexes formation. In 96 hours after adrebalectomy additional cortical tissue already responds to ACTH and accordingly stress after pretreatment with ACTH results in a greater increase of non=enzymatic fibrinolytic activity than that without ACTH.     

Molecular genetic analysis of the biological properties of highly pathogenic influenza A/H5N1 virus strains isolated from wild birds and poultry during epizooty in Western Siberia (July 2005)

The full-size genomes of 2 highly pathogenetic avian influenza (HPAI) virus strains isolated from a wild great-crested grebe (A/Grebe/Novosibirsk/29/05) and a domestic duck (A/Duck/Novosibirsk/56/05) in the tract of the Chany hollow, Barabino forest-steppe (Novosibirsk Region) during the epizootic outbreak in the summer of 2005. The reproductive properties of these strains successively increase in the series of cell lines BHK-2 --> LEH --> Vero-E6 --> MDCK --> PS. A/Grebe/Novosibirsk/29/05 and A/Duck/Novosibirsk/56/05 were shown to be genetically close in all genomic segments to both each other and a group of HPAI/H5N1 A/Qinghai 05 strains isolated from wild birds on the Kukunor Lake in the northwestern province of Tsinkhai, China, in May 2005. All the above strains have the HPAI/H5-specific amino acid sequence of a proteolytic cleavage site (PQGERRRKKRGLF) with Lys-627 in the protein PB2 (which is associated with increased virulence to mammalian cells), Glu-92 in the protein NS1 (that suppresses an antiviral response in the host), Ser-31 in M2 (that is a marker of rimantadine/amantadine sensitivity), 20-member amino acid deletion in the protein NA (positions 49-68) that is a marker of affiliation to the so-called genotype Z and of increased tropism to poultry.