Modifying Distant Effect of High Dilutions of Inorganic and Biological Substances.

It is known that highly diluted substances can exert a modifying effect on the initial substances without direct contact with them (distant interaction). The capability of high dilutions of IFNγ and Na2SO4 for the distant modifying effect was studied by the method of terahertz spectroscopy. Statistically significant differences were shown between terahertz characteristics of the initial solution of IFNγ protein and solution that had interacted with high dilutions of IFNγ; in case of sodium sulfate, no such differences were detected. Thus, high dilutions exert a distant modifying effect on the initial substances with complex spatial structure typical of biological molecules.

Study of the Effects of Highly Diluted Sodium Sulfate and Interferon-Gamma.

High dilutions of solutions containing extremely small amounts of the initial substance can modify the biological effects of the initial substance molecules. Using terahertz spectroscopy, we studied the possibility of modifying the physicochemical properties of the initial substance by adding high dilutions of high-molecular-weight (IFNγ) and low-molecular-weight (Na2SO4) compounds. In addition, the modifying effect produced by high dilutions of a low-molecular electrolyte (a solution of Na2SO4 salt) on the initial substance was confirmed by conductometry. This method allows measuring electrical conductivity that also depends on the physicochemical properties of the solution, namely, the number of ions and velocity of their movement. Statistically significant differences were shown between terahertz and conductometric characteristics of the initial solution (inorganic salt Na2SO4 or a protein IFNγ) and a solution, where high dilutions of the same substances were added in different concentrations. Interestingly, the differences were more pronounced for the biological molecule. Thus, it has been shown that high dilutions can change the properties of the initial solution; the effect is more pronounced for the protein solution.

[The intraoperative prophylaxis of local ischemical brain damage in neurosurgical patients with cerebral aneurysm]. / Intraoperatsionnaia profilaktika lokal'nogo ishemicheskogo povrezhdeniia golovnogo mozga u neirokhirurgicheskikh patsientov s tserebral'noi anevrizmoi.

AIM: To study the effectiveness of intraoperative administration of Cytoflavine for the prevention of ischemic brain injury during cerebral aneurysm (CA) clipping with temporary occlusion of the leading artery under general anesthesia. MATERIAL AND METHODS: The prospective cohort single-center study included 40 patients with CA ( the main group - 27 patients with intraoperative administration of cytoflavine; the comparison group -13 patients without use of cytoflavine), who underwent aneurism clipping with temporary occlusion of the afferent artery. We assesed the intraoperative state of the brain, the time of awakening and extubation of patients after surgery, neurological deficit and local ischemic changes in the area of surgery according to the CT of the brain in the early postoperative period, resuscitation bed-day and the relationship of these indicators with the duration of temporary occlusion of the afferent artery in the selected groups of patients. RESULTS: In intergroup comparison, patients of the main group treated with intraoperative cytoflavin showed a reduction in the time of awakening (p=0.013) and the time of extubation (p=0.01) both with temporary occlusion of the afferent artery and in patients without temporary occlusion (p<0.05). The duration of resuscitation bed-day decreased in the main group of patients receiving intraoperatively cytoflavine (p=0.01), as well as in patients in the comparison group without temporary occlusion (p<0.05). CONCLUSION: Temporary occlusion of the afferent artery with short intervals of vessel occlusion in combination with intraoperative intravenous administration of cytoflavine expands the tolerability to artery occlusion in patients operated in the 'cold' period, reduces the possibility of neurological deficit, reduces the recovery period and resuscitation bed-day after surgical clipping CA.

Ergoferon Increases IL-2 Production by Activated Lymphocytes.

We studied the effects of Ergoferon on the production of antiviral cytokine IL-2 by type 1 CD4+T cells. Preincubation of Jurkat cells with Ergoferon increased IL-2 secretion by these cells after stimulation with phorbol 12-myristate 13-acetate/ionomycine in comparison with the placebo group. The data prove that Ergoferon is capable of activating cell cascades involved in the realization of the antiviral immune response.

[Amino acid chloramines and chlorimines as antiplatelet agents: reactive properties and mechanism of action].

Oxidative modifications of thiols, disulfide, and thioester atomic groups in proteins, peptides, and amino acids induced by chloramines or chloramine derivatives of amino acids and other reactive oxidants are considered. In the case of disulfide and thiol groups, production of sulfur-reactive groups may take place, such as disulphide S-oxides and sulphenic groups. Various chloramines and chloramines differently modify sulfur-containing groups. For example, N,N-dichlorotaurine rapidly modifies the thiolgroup in reduced glutathione and N-chloroglycine readily oxidizes the thioester group in methionine. Amino acid chloramines inhibit platelet aggregation by modifying S-containing centres. Autodecay of amino acid chloramines does not affect aggregation as follows from the absence of positive correlation between chloramines decay rate and antiplatelet activity. N,N-dichlorotaurine and its chlorimine derivatives are characterized by high stability and have good prospects as potential antiaggregants.

[The relatioship between decomposition of amino acid chloramines and their structures].

Rate constants of the decomposition of monoamine alpha-amino acid chloramine derivatives were determined by a spectrophotometeric method. Several amino acid chloramines with elevated stability have been found. These included n-chloroglycine, n-chlorovaline, n-chlorothreonine, and n-chloroisoleucine. Their molecular structures are characterized by some characteristic feature at the beta-position. In the case of glycine chloramine, carbon atom at this position is absent, and the chloramine derivatives of three other amino acids possess branched chains. Partial atomic charges of the electrostatic potential (Wang-Ford) for chloramines of alpha-amino acids were computed using the semiempirical quantum-mechanical method AM1. The chloramines with elevated stability have high positive sums of charges of three carbon atoms that are atoms at alpha- and beta-positions and a carboxyl group atom. High partial charge also was obtained for one carbon atom at the beta-position. These computational values may be employed for prediction of the stability of designed amino acid chloramines. One of the important predictions is that the highest atomic charges and stabilities are characteristics of the amino acid chloramines, in which all hydrogen atoms at the beta-position are replaced by carbon-hydrogen chains or hydroxyl groups.

Antiaggregant effect of taurine chloramines in the presence of serum albumin.

The effects of taurine chloramine derivatives on initial aggregation of isolated platelets suspended in buffered saline were studied. Inhibition of ADP-induced aggregation in pure cell suspension depended on the structure of chloramine antiaggregants. The most effective of them was N,N-dichlorotaurine; its concentration needed for 50% inhibition of aggregation was about 0.1 mM. Weaker antiaggregants N-chloro-N-methyltaurine and N-chlorotaurine in a final concentration of 0.5 mM reduced platelet aggregation by only 10%. The studied chloramines considerably differed by their characteristics (velocity of the reaction with sulfur-containing groups of atoms). N,N-dichlorotaurine exhibited the weakest reactivity with methionine thioester group. In turn, the velocity constant with reduced glutathione was by 2-3 orders of magnitude higher than that of other chloramines. Antiaggregant effect of taurine chloramine derivatives was 2-fold higher in the presence of serum albumin, presumably due to special interactions of taurine chloramines in complex with albumin with platelets.

Antiaggregant effects of biogenic chloramines.

Alanine and taurine sharply potentiate antiaggregant effects of hypochlorite on platelets in platelet-rich plasma. This effect is determined by more pronounced action of chloramine derivatives, products of interaction of added amino acids with hypochlorite. Platelets are more sensitive to the inhibitory effects of amino acid chloramine derivatives (biogenic chloramines) compared to erythrocytes and neutrophils. The antiaggregant effects of biobenic amines, as covalent platelet inhibitors, in platelet-rich plasma are characterized by their increased reaction capacity with molecular targets in cells. Quantitative parameter of this initial selectivity (ratio of rate constant of inactivation of platelet receptors to rate constant of side reaction with plasma proteins) far surpasses 1. N,N-Dichlorotaurine is a perspective antiaggreant among the studied biogenic chloramines. This agent is stable and exhibits specific pharmacological activity in all test systems, including animal model of thrombosis.