Influence of natural polysaccharides on the morphology and properties of hybrid vaterite microcrystals.

Co-precipitation of biopolymers into calcium carbonate crystals changes their physicochemical and biological properties. This work studies hybrid microcrystals of vaterite obtained in the presence of natural polysaccharides, as carriers for the delivery of proteins and enzymes. Hybrid microcrystals with dextran sulfate, chondroitin sulfate, heparin, fucoidan, and pectin were obtained and compared.

Incorporation of Pectin into Vaterite Microparticles Prevented Effects of Adsorbed Mucin on Neutrophil Activation.

The application of vaterite microparticles for mucosal delivery depends on their interaction with mucin and immune cells. As we have shown previously, the binding of mucin onto particles enhances the generation of reactive oxygen species by neutrophils. The attenuation of the pro-oxidant effect of the bound mucin through the modification of vaterite could improve its biocompatibility.

Antiplatelet Action of Chloramine Derivatives of Adenosine Phosphates and Their Chemical Activity in Relation to Sulfur-Containing Compounds.

We studied the properties of N6-chloroadenosine phosphates (ATP, ADP, and AMP chloramines) as compounds with potentially increased antiplatelet efficacy determined by their binding to the plasma membrane of platelets. Chloramine derivatives of ATP, ADP, and AMP do not differ in their optical absorption characteristics: their absorption spectra are in the range of 220-340 nm with a maximum at 264 nm. Chloramines of adenosine phosphates are characterized by high reactivity with respect to thiol compounds.

[Molecular characteristics and prediction of the reactive properties of the N-chlorotaurine analogs].

A number of molecular characteristics for the N-chlorotaurine structural analogs, amino acid chloramines and relative compounds have been computed by the ab initio method B3LYP/6-31G. In particular, the characteristics were the Mulliken atomic charges for the chloramine part and its adjacent atoms. A quantitative measure of the capabilities of the chloramines to react with the methionine sulfide group or sulfhydryl group of reduced glutathione was their reaction rate constants.

Inhibition of plasma coagulation and platelet aggregation with structural analogs of taurine chloramine.

We studied the effects of amide and N-alkyl analogs of taurine chloramine on rabbit plasma coagulation and platelet aggregation. Alkyl analog N-isopropyl-N-chlorotaurine produced greater increase in plasma coagulation time after its activation by the contact method or with thrombin than amide analog N-propionyl-N-chlorotaurine. In case of coagulation induced by the tissue factor, the test analogs produced similar effect.

[Covalent chloramine inhibitors of blood platelet functions: computational indices for their reactivity and antiplatelet activity].

The quantum mechanics computation of the reactivities of chloramine derivatives of amino acids and taurine has been accomplished. A pair of computational indices that reflect a predisposition of alpha amino acid chloramines to chemical decay have been revealed. One of the indices was the dihedral angle for the chain of four atoms: carbons at beta- and alpha-positions, carbon of the carboxyl group, and carbonyl oxygen.

Anticoagulant effects of thioanalogs of thrombin-binding DNA-aptamer and their stability in the plasma.

In order to create effective therapeutically significant oligonucleotide structures, a series of analogs of thrombin-binding aptamer d(GGTTGGTGTGGTTGG) containing thiophosphoryl substitutions were synthesized. The anticoagulation effects of the resultant thrombin-binding aptamer analogs were evaluated and the effects of local thiomodifications on their structure and function were studied, including the effects on stability in blood plasma and resistance to DNA nucleases. A promising modified oligonucleotide (LL11) was found with the structure modified only in TT loops.

[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.

[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.

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.

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.

[Initial selectivity of the antiplatelet covalent action of biogenic chloramines on platelet-rich plasma].

To describe in full the peculiarities of the antiplatelet action of covalent inhibitors on platelet-rich plasma, we have proposed to take into account the initial selectivity that determines the elevated efficacy of inactivation of platelet molecular target (receptor). The quantitative index of initial selectivity is the ratio of rate constant of inactivation of the platelet molecular target to the rate constant of the chemical reaction of an inhibitor with reactive atomic groups in plasma proteins. For the important case of the domination of the inhibitor expenditure in the reaction with plasma proteins, a formula was derived which depicts the dependence of the share of inactivated targets on the concentration of the inhibitor introduced and reactive atomic groups contained in plasma.

[Mechanism of action of biogenic chloramines and hypochlorite on initial aggregation of blood platelets].

The antiaggregant action of two reactive oxidants N,N-dichlorotaurine (chloramine of biogenic type) and sodium hypochlorite on the initial ADP-induced aggregation of rabbit blood platelets has been studied. Platelet aggregation in the reconstructed platelet-rich plasma (PRP) was measured by the nephelometric method, and the aggregation index was an increase in the intensity of small-angle light scattering. The introduction of chloramine at comparatively small concentrations (no greater than 1 mM active chlorine) directly into the reconstructed platelet-rich plasma induces the suppression of the initial aggregation (formation of small aggregates) several times stronger than in the case of its preliminary incubation with plasma alone.

[Luminol-enhanced chemiluminescence of rabbit polymorphonuclear leukocytes: the nature of oxidants that directly induce luminol oxidation].

The present work deals with the reaction pathways, including the formation of hydroxyl radicals and chloroamines, which lead to luminol chemiluminescence caused by hypochlorite generation in a suspension of stimulated rabbit polymorphnonuclear leukocyte. Luminol-enhanced (0.02 mM) chemiluminescence of leukocytes stimulated by phorbol 12-myristate 13-acetate does not change in the presence of dimethyl sulfoxide at moderate concentrations (0.

[Chemiluminescence in a stimulated polymorphonuclear leukocytes--luminol system: suppression by thiols].

The effect of some scavengers of thiol nature, which eliminate all reactive oxygen species and oxidants with reactive chlorine, on the luminol-enhanced chemiluminescence of polymorphonuclear leukocytes was studied. The use of two scavengers of this type (penetrating and not penetrating into the cell) made it possible to separate the luminescence of cell structures from the luminescence generated by oxidants in the surrounding medium. It was found that about a half of luminol luminescence is due to its oxidation in the medium surrounding the cell, and it is completely inhibited by the nonpenetrating reduced glutathione.

Structure and oxidation capacity of amino acid chloramine derivatives and their effects on platelet aggregation.

Comparison of antiaggregation capacity of N-chloramine acids with different position of the chloramine group in the molecule showed that in the most efficient compounds the distance between the chloramine and carboxyl groups was 3-5 carbon atoms. This feature of antiaggregation activity was not related to the difference in oxidation capacity of N-chloramine acids. It was hypothesized that the revealed structural dependence of antiaggregation activity of N-chloramine acids is determined by the structure of platelet membrane, in particular, the presence of a negatively charged group near the site of interaction between N-chloramine acids and platelet membrane.

[Chemiluminescence of the polymorphonuclear leukocytes-luminol system in the presence of biogenic chloramines].

It was demonstrated that N-chlorphenylalanine and other chloramines strengthen sharply chemiluminescence in the polymorphonuclear leukocytes (PML)-luminol system without special activation of cells. The intensity of chemiluminescence is higher than the intensity of luminol solution emission induced by N-chlorphenylalanine. But it was nearly equal to chemiluminescence intensity of a mixture of luminol, N-chlorphenylalanine and 20-30 nM H2O2.

Antithrombotic activity of N,N-dichlorotaurine on mouse model of thrombosis in vivo.

Intravenous injection of chloramine derivatives of amino acids and taurine reduced the mortality rate in mice with thrombosis induced by intravenous injection of ADP or collagen-epinephrine mixture. Intravenous injection of N,N-dichlorotaurine caused 50% inhibition of platelet aggregation induced by ADP and measured in the platelet-enriched plasma in vitro. The antithrombotic effect of chloramine derivatives of amino acids and taurine is related to their ability to suppress functional activity of platelets.

[Kinetic characteristics of luminol chemiluminescence caused by chloramine compounds].

The decaying part of the kinetic curves of luminol chemiluminescence (0.02 mM) induced by N-chlorphenylalanine is approximated by an exponential dependence, which varies insignificantly as chloramine concentration is changed from 0.2 to 0.

[Chemiluminescence in oxidation of luminol by chloramine derivatives of biogenic compounds].

Chloramine derivatives of amino acids induce chemiluminescence of a luminol solution. The chemiluminescence is more prolonged than the emission of luminol produced by hypochlorite. Persistent chemiluminescence also appears under the action of hypochlorite on a mixture of luminol and amino acids.

Free-radical and cyclooxygenase-catalyzed lipid peroxidation in membranes of blood cells under UV irradiation.

The data on the role of lipid peroxidation in the effects of UV irradiation of blood are reviewed. Lipid photoperoxidation in blood cells is the result of photochemical transformation of lipid hydroperoxides, both existing and newly formed ones, into free radicals and direct photolysis of photooxidants. Dark lipid autoperoxidation is also induced by UV radiation.

[Difference in inhibitory actions of products of the myeloperoxidase- catalyzed reaction on initial aggregation of activated platelets].

Inhibition of the initial aggregation of isolated rabbit platelets was studied on two types of their stimulation. The stimuli were either ADP, which was also capable to induce cell rounding, or adrenaline, and CaCl2, which acted without cell rounding. When platelets are stimulated by adrenaline or calcium chloride, sodium hypochlorite enhances the anti-aggregatory effect: at a concentration of about 10 microM the aggregation is reduced by 50%.

[The anti-aggregatory effect of chloramine derivatives of amino acids on platelets in the presence of plasma].

Rabbit platelet aggregation induced by ADP is suppressed equally by the group of the chloramine derivatives of uncharged amino acid with the high molecular masses (N-chlorphenylalanine, N-chlorglutamine, N-chlorleucine). The effects of the derivatives of other uncharged amino acids are different, the inhibition degree increasing sharply at the decrease of molecular mass of amino acid chloramines. Ratio of the rate constant for the reaction of these chloramines with platelets and the rate constant for the reaction with plasma components raises exponentially at the molecular mass reduction.