Anxiolytic agent afobazole (10 mg/kg intraperitoneally) 24 h after ischemia restores impaired balance of excitatory and inhibitory amino acids in the striatum of mongrel rats, normalizes their content to control levels, and activates endogenous taurine-dependent system of neuroprotection.

Novel mono- and dicationic pyrimidinic surfactants are synthesized and their aggregation behavior is studied by methods of tensiometry and nuclear magnetic resonance (NMR) self-diffusion. To estimate their potentiality as gene delivery agents, the complexation with oligonucleotides (ONus) is explored by dynamic light scattering (DLS) and zeta-potential titration methods and ethidium bromide exclusion experiments. Bola-type pyrimidinic amphiphile (BPM) demonstrates rather a weak affinity to ONus. Although it induces mixed associations with ONus, only slight charge compensation changes occur at a large excess of bola, with no recharging reached. Similarly, the ethydium bromide exclusion study reveals a slow increase in the binding capacity toward an ONu with an increment in BPM concentration. The monocationic pyrimidinic surfactant (MPM) and its gemini analogue (GPM-1) are ranked as intermediates in both their aggregative activity and complexing properties toward ONus. They both form mixed associates with ONus well below the critical micelle concentrations (cmcs) of 2 and 15 mM respectively. However, GPM-1 has a much lower isoelectric point at the molar ratio surfactant/ONu r~1 compared to r~3 for MPM. This probably indicates a larger electrostatic contribution to the ONu complexation in the case of GPM-1. The most hydrophobic pyrimidinic surfactant (GPM-2), bearing three alkyl tails, demonstrates enhanced aggregative activity and binding capacity toward ONus as compared to former pyrimidinic surfactants. Due to effective aggregative (low cmc of 0.04 mM) plus binding properties (fraction of bound ONu β=0.76 at r=2.5), GPM-2 may be ranked as a promising agent for wider biological applications.

Avian schistosome Trichobilharzia szidati is a member of the largest genus within the family Schistosomatidae (Trematoda). Population genetic structure of Trichobilharzia spp. schistosomes, causative agents of cercarial dermatitis in humans, has not been studied yet. The knowledge of the genetic structure of trichobilharzian populations is essential for understanding the host-parasite coevolutionary dynamics and epidemiology strategies. Here we examined genetic diversity in three geographically isolated local populations of T. szidati cercariae inhabiting Russia based on nuclear (randomly amplified polymorphic DNA, RAPD) and mt (cox1) markers. We analyzed T. szidati cercariae shed from seven naturally infected snails of Lymnaea stagnalis. Using three random primers, we demonstrated genetic variation among populations, thus posing genetic structure across geographic sites. Moreover, T. szidati cercariae have been genetically structured among hosts (infrapopulations). Molecular variance analysis was performed to test the significance of genetic differentiation within and between local populations. Of total parasitic diversity, 18.8% was partitioned between populations, whereas the higher contribution (48.9%) corresponds to the differences among individual cercariae within infrapopulations. In contrast to RAPD markers, a 1,125-bp fragment of cox1 mt gene failed to provide any significant within-species structure. The lack of geographic structuring was detected using unique haplotypes which were determined in the current work for Moscow and Western Siberian local populations as well as obtained previously for European isolates (Czech Republic and Germany). All T. szidati/Trichobilharzia ocellata haplotypes were found to be mixed across their geographical origin.

A new macrocyclic bolaamphiphile with thiocytosine fragments in the molecule (B1) has been synthesized and advanced as perspective platform for the design of soft supramolecular systems. Strong concentration-dependent structural behavior is observed in the water-DMF (20% vol) solution of B1 as revealed by methods of tensiometry, conductometry, dynamic light scattering, and atomic force microscopy. Two breakpoints are observed in the surface tension isotherms. The first one, around 0.002 M, is identified as a critical micelle concentration (cmc), whereas the second critical concentration of 0.01 M is a turning point between the two models of the association involved. Large aggregates of ca. 200 nm are mostly formed beyond the cmc, whereas small micelle-like aggregates exist above 0.01 M. The growth of aggregates between these critical points occurs, resulting in a gel-like behavior. An unusual decrease in the solution pH with concentration takes place, which is assumed to originate from the steric hindrance around the B1 head groups. Because of controllable structural behavior, B1 is assumed to be a candidate for the development of biomimetic catalysts, nanocontainers, drug and gene carriers, etc.

In vitro radioligand assay revealed interaction of afobazole with sigma(1)-receptors (Ki=5.9x10(-6)M). Translocation of sigma(1)-receptors from the endoplasmic reticulum to the outer membrane was demonstrated by confocal microscopy. Experiments were performed on the model of HT-22 immortalized hippocampal cells after incubation with afobazole in a concentration of 10(-8)M.

Selective anxiolytic afobazole (1 mM) inhibits monoamine oxidase A activity in mitochondria from rat brain and liver (IC(50)0.36 and 0.43, respectively). Effect of the compound does not depend on the time of preincubation with mitochondria. Triple washout of mitochondria is followed by complete recovery of initial enzyme activity.

New amphiphilic pyrimidinic (AP) compounds with two ammonium head groups and different kinds of counterions, inorganic bromide anions (APB) and hydrophobic tosylate anions (APT) were synthesized. Self-organization in these systems has been studied by methods of tensiometry, conductometry, potentiometry and NMR spectroscopy. The critical micelle concentrations (cmc's) of bola-type surfactants are only a little lower than those of cetyltrimethylammonium (CTA) analogues. For both pairs APB/CTAB and APT/CTAT the counterion binding is stronger for the conventional cationic surfactants as compared to 'bola' pyrimidinic surfactants. Unlike the CTAT micelles no sharp micellar growth occurs with the APT concentration. The geometry of AP compounds is assumed to be mainly responsible for the above finding. A branched molecular architecture prevents a close packing of the monomers in the bulk solution and at the interface producing a steric hindrance around the head groups.

Here we report the clouding phenomenon, conductivity,(1)H NMR spectroscopy and dynamic light scattering data of mixed sodium dodecylsulfate-calix[4]resorcinarene micellar solutions in combination with tetrabutyl-, tetraethyl-, tetramethylammonium bromides and choline chloride. The NMR data reveal tight (the binding constant is about 10(4)) guest-host binding of calix[4]resorcinarene in alkaline conditions with tetraethyl-, tetramethylammonium and choline cations. This binding occurs at rather small concentrations of the external quaternary salts (0-0.0005 M) and leads to dramatic increase of the cloud point temperature. The obtained data are discussed in the correlation with the micellar size changes, caused by the ion exchange due to the variation of quaternary salt concentrations.

New amphiphilic pyrimidinic macrocycles (APMs) with two (APM-1) and three (APM-2) decyl tails have been synthesized by quaternization of the bridged N. Complex examination of the APM-based systems with the help of tensiometry, conductometry, dynamic light scattering, and UV and NMR spectroscopy provides evidence for their aggregation. Calculations based on surface tension isotherms and on packing parameter considerations make it possible to assume a lamellar packing of macrocycles when aggregating. Marked differences in the aggregation behavior of APM-1 and APM-2 have been found. The additives of polyethylenimine (PEI) exert little influence on the critical micelle concentration (cmc) of APM-1, while in the APM-2/PEI systems there occurs a pronounced decrease in the cmc and also a ca. 2-fold decrease in the surface area per molecule. The APM-based assemblies are explored as nanoreactors for the hydrolysis of O-alkyl O-p-nitrophenyl (chloromethyl)phosphonates (alkyl = ethyl, hexyl). The kinetic study reveals a minor rate effect of the APM-1-based systems. In the APM-2-based systems an acceleration of the hydrolysis of both phosphonates occurs as compared to the uncatalyzed process. Within the APM-2 --> APM-2/PEI --> APM-2/PEI/La(III) series, due to the cooperative contributions of the supramolecular, polymer, and homogeneous catalysis, an increase in the catalytic effect is observed from 30 times to 3 orders of magnitude as compared to that of the basic hydrolysis of the substrates.