Cisplatin and progesterone separate and combined action on rat brain nuclear phospholipids content.

The antitumor agent cisplatin and steroid hormone progesterone separate and combined action on content of total phospholipids and their individual classes in nuclei from rat brain cells were investigated. Cisplatin and progesterone exhibit their own characteristic properties, when used separately. Cisplatin reduces, and progesterone, on the contrary, increases the content of total phospholipids. When used together, the effects of these drugs are summed up. Cisplatin reduces the content of all 7 individual phospholipids found in rat brain nuclear preparations. Progesterone, on the other hand, increases the content of 5 classes of phospholipids. The combined use of cisplatin and progesterone restores 5 classes of nuclear phospholipids to the baseline level, and increases the quantity of 2 classes. The obtained results are discussed in terms of antagonistic effects of studied drugs, which can help in reducing undesirable side effects of cisplatin in case of combined use of antitumor drug and steroid.

The effects of ultraviolet, gamma- and X-ray irradiation on the growth, antibacterial activity and radio-protective of Lactobacillus rhamnosus.

Ionizing radiation is widely applied in food production as preservation technology and for correction of the gut microbiome of cancer patients, rescuers, astronauts etc. Lactic acid bacteria (LAB) can be used for the same reason. The main goal of this study was to investigate the effect of irradiation on some activities of Lactobacillus rhamnosus MDC 9661 and its effect on the survival of irradiated rats. The results indicate that both ultraviolet (during 45 min) and X-ray irradiations (with 2 Sv) decreased the CFU and the antibacterial activity of the strain. Higher than 700 Sv dose of X-ray irradiation resulted in the total inhibition of antibacterial activity with the total reduction of colony forming units less than 10 cells ml-1 , while irradiated with 1000 Sv dose L. rhamnosus MDC 9661 did not lose its proteolytic activity. It was also shown that L. rhamnosus MDC 9661 was not immunogenic in the organism of the rats and cannot lead to the development of autoimmune responses. L. rhamnosus MDC 9661 demonstrated the necessary properties for probiotics and can be effectively used for the correction of the gut microbiome of all target groups. The co-aggregation of the cells is one of the mechanisms for resistance of LAB to irradiation.

Applicability of the absence of equilibrium in quantum system fully coupled to several fermionic and bosonic heat baths.

The time evolution of an occupation number is studied for a fermionic or bosonic oscillator linearly fully coupled to several fermionic and bosonic heat baths. The influence of the characteristics of thermal reservoirs of different statistics on the nonstationary population probability is analyzed at large times. Applications of the absence of equilibrium in such systems for creating a dynamic (nonstationary) memory storage are discussed.

Non-Markovian dynamics of quantum systems coupled with several mixed fermionic-bosonic heat baths.

For the fermionic or bosonic oscillator fully coupled to several heat baths with mixed statistics, the analytical expressions for the occupation numbers are derived within the non-Markovian quantum Langevin approach. Employing two or three heat baths and the Ohmic dissipation with Lorenzian cutoffs, the role of statistics of the system and heat baths in the dynamics of the system is studied.

Crystal structures and vibrational spectra of L-argininium(2+) bis(tetrafluoroborate) and L-argininium(2+) bis(perchlorate).

In the present work crystal structures of (L-ArgH2)(BF4)2 (I) and (L-ArgH2)(ClO4)2 (II) isostructural salts have been determined. They crystallize in triclinic system with space group P1 and Z = 1. Structure features of the (I) and (II) were compared with respective data of previously known (L-ArgH)(BF4) and (L-ArgH)(ClO4) salts with singly charged L-argininium(+) cation. Infrared and Raman spectra of the (I) and (II) are compared with spectra of (L-ArgH)(BF4) and (L-ArgH)(ClO4) salts. The presence of cation and anions and hydrogen bonds between them are reflected in the IR and Raman spectra. The crystals (I) and (II) exhibit second harmonic generation activity.

Effects of iron oxide (Fe3 O4 ) nanoparticles on Escherichia coli antibiotic-resistant strains.

AIMS: Antibiotic resistance of different bacteria requires the development of alternative approaches for overcoming this phenomenon. The antibacterial effects of iron oxide (Fe3 O4 ) nanoparticles (NPs) (from 50 to 250 µg ml-1 ) on Escherichia coli antibiotic-resistant strains have been aimed. METHODS AND RESULTS: The study was performed with ampicillin-resistant E. coli DH5α-pUC18 and kanamycin-resistant E. coli pARG-25 stains. Specific growth rate of bacteria (µ), lag phase duration and colony-forming units (CFU) were determined to evaluate growth properties. Fe3 O4 NPs (average size of 10·64 ± 4·73 nm) coated with oleic acid and synthesized by modified co-precipitation method were used. The medium pH, H+ efflux, membrane H+ conductance, redox potential determinations and H2 yield assay were done using potentiometer methods. Growth properties were changed by NPs in concentration-dependent manner. NPs decreased (up to twofold) H+ -fluxes through bacterial membrane more in E. coli in the presence of the N,N'-dicyclohexylcarbodiimide, inhibitor of ATPase, indicating that antibacterial activity of these NPs was connected with ATP-associated metabolism. Membrane-associated H2 production was lowered up to twofold. Moreover, the synergetic interactions of NPs and antibiotics were found: combination of NPs and antibiotics provided the higher H+ conductance, lower H+ -fluxes and H2 yield. CONCLUSIONS: Fe3 O4 NPs can be suggested as alternative antibacterial agents, which can substitute antibiotics in different applications. SIGNIFICANCE AND IMPACT OF THE STUDY: The antibacterial effects of Fe3 O4 NPs on the growth properties and membrane activity of E. coli antibiotic-resistant strains have been demonstrated. These NPs have potential as antibacterial agents, which can substitute for antibiotics in bacterial disease treatment in biomedicine, pharmaceutical and environmental applications.

Non-Markovian dynamics of fermionic and bosonic systems coupled to several heat baths.

Employing the fermionic and bosonic Hamiltonians for the collective oscillator linearly FC-coupled with several heat baths, the analytical expressions for the collective occupation number are derived within the non-Markovian quantum Langevin approach. The master equations for the occupation number of collective subsystem are derived and discussed. In the case of Ohmic dissipation with Lorenzian cutoffs, the possibility of reduction of the system with several heat baths to the system with one heat bath is analytically demonstrated. For the fermionic and bosonic systems, a comparative analysis is performed between the collective subsystem coupled to two heat baths and the reference case of the subsystem coupled to one bath.

Genetic differentiation between upland and lowland populations shapes the Y-chromosomal landscape of West Asia.

Y-chromosomal variation in West Asian populations has so far been studied in less detail than in the neighboring Europe. Here, we analyzed 598 Y-chromosomes from two West Asian subregions-Transcaucasia and the Armenian plateau-using 40 Y-SNPs and 17 Y-STRs and combined them with previously published data from the region. The West Asian populations fell into two clusters: upland populations from the Anatolian, Armenian and Iranian plateaus, and lowland populations from the Levant, Mesopotamia and the Arabian Peninsula. This geographic subdivision corresponds with the linguistic difference between Indo-European and Turkic speakers, on the one hand, and Semitic speakers, on the other. This subdivision could be traced back to the Neolithic epoch, when upland populations from the Anatolian and Iranian plateaus carried similar haplogroup spectra but did not overlap with lowland populations from the Levant. We also found that the initial gene pool of the Armenian motherland population has been well preserved in most groups of the Armenian Diaspora. In view of the contribution of West Asians to the autosomal gene pool of the steppe Yamnaya archaeological culture, we sequenced a large portion of the Y-chromosome in haplogroup R1b samples from present-day East European steppe populations. The ancient Yamnaya samples are located on the "eastern" R-GG400 branch of haplogroup R1b-L23, showing that the paternal descendants of the Yamnaya still live in the Pontic steppe and that the ancient Yamnaya population was not an important source of paternal lineages in present-day West Europeans.

Photo-induced processes in collagen-hypericin system revealed by fluorescence spectroscopy and multiphoton microscopy.

Collagen is the main structural protein and the key determinant of mechanical and functional properties of tissues and organs. Proper balance between synthesis and degradation of collagen molecules is critical for maintaining normal physiological functions. In addition, collagen influences tumor development and drug delivery, which makes it a potential cancer therapy target. Using second harmonic generation, two-photon excited fluorescence microscopy, and spectrofluorimetry, we show that the natural pigment hypericin induces photosensitized destruction of collagen-based tissues. We demonstrate that hypericin-mediated processes in collagen fibers are irreversible and may be used for the treatment of cancer and collagen-related disorders.

Interaction between hypericin and hemoglobin.

In the present work the hypericin interaction with hemoglobin was studied by absorption and fluorescence spectroscopy both under incubation in dark and visible light exposure. An absorption reduction in Soret band of hemoglobin (407 nm) was revealed under the photodynamic influence and incubation in dark with hypericin that had hypericin concentration and time dependent manner. Hypericin reduced the intensity of the hemoglobin emission peaks at 334 and 421 nm, correlating with hypericin concentration, incubation and irradiation time. An obvious increase in electrophoretic mobility of hemoglobin was observed under the incubation with hypericin. Simultaneously, a partial conversion of hemoglobin to met-hemoglobin and a pH decrease in hemoglobin solution were detected. Structural changes of hemoglobin caused by hypericin were accompanied by a change in peroxidase activity of the protein. Thus under the hypericin influence hemoglobin properties as a hydrogen peroxide detector could be improved and an effective determination of peroxide formation could be achieved. This makes hemoglobin an attractive 'recognition' element for construction of third-generation biosensors.

The novel inhibitors of serine proteases.

Thirty optically active nonprotein alpha-amino acids and peptides based thereon have been screened for their ability to interact with bovine trypsin and proteinase K from Tritirachium album Limber, which belong to the group of serine proteases. Both structure-based drug design approach and determination of enzyme activity have been used to identify low molecular weight inhibitors of trypsin and proteinase K. Compounds have been selected that according to the docking analysis were able to interact with trypsin and proteinase K. Following the docking analysis measurement of enzymes activity (2R,3S)-beta-hydroxyleucine and (2S,3R)-beta-hydroxyleucine inhibited both enzymes activity, whereas (S)-alpha-methyl-beta-phenylalanine, (R)-alpha-methyl-beta-phenylalanine, (S)-allylglycine, (R)-allylglycine, (S)-alpha-allylalanine, (R)-alpha-allylalanine and allo-O-ethylthreonine inhibited only proteinase K; and N-formyl-(S)-methionyl-(2S,3R)-hydroxyleucine, N-formyl-(S)-methionyl-(2R,3S)-hydroxyleucine, N-formyl-(S)-methionyl-(S)-allylglycine and N-formyl-(S)-methionyl-(R)-allylglycine inhibited trypsin. It has been shown that inhibition of trypsin by (2R,3S)-beta-hydroxyleucine and N-formyl-(S)-methionyl-(2R,3S)-hydroxyleucine is of a competitive mode.

Comparative study of Rhodiola preparations on behavioral despair of rats.

The antidepressant-like activity of an extract of the roots of Rhodiola rosea (RR), its combination with piperine containing extract (RPE), pure substances isolated from Rhodiola, such as rhodioloside, rosavin, rosin, rosarin, tyrosol, cinnamic alcohol, cinnamaldehyde and cinnamic acid has been assessed in laboratory animals through application of the Porsolt behavioural despair assay. RR increased the swimming time of rats in a dose dependent manner (ED50=7 mg/kg) and, when administered at 20mg/kg, exhibited a stronger anti-depressant type effect than either imipramine (at 30 mg/kg) or an extract of Hypericum perforatum (at 20mg/kg). Rhodioloside, and tyrosol were identified as active principles of the extract, whereas rosavin, rosarin, rosin, cinnamic alcohol, cinnamaldehyde, cinnamic acid were inactive. A fixed combination of rhodioloside, rosavin, rosarin and rosin was more active than any of the individual components alone, indicating a synergistic effect of the ingredients in RR extract. Piperine in combination with Rhodiola (RPE) distorts pharmacological effect of Rhodiola most probably due to changes of pharmacokinetic profile of rhodioloside and rosavin. RPE cannot provide predictable therapeutic effect due to herb-herb interaction. Moreover, concomitant treatment of RPE with other drugs should also be excluded due to drug-piperine interaction.

Estimate of B(B(over) -->Xgamma) at O(alpha(s)2).

Combining our results for various O(alpha[s]) corrections to the weak radiative B-meson decay, we are able to present the first estimate of the branching ratio at the next-to-next-to-leading order in QCD. We find B(B[over ]-->X[s]gamma)=(3.15+/-0.23) x 10(-4) for Egamma>1.6 GeV in the B[over ]-meson rest frame. The four types of uncertainties:nonperturbative (5%), parametric (3%), higher-order (3%), and m(c)-interpolation ambiguity (3%) have been added in quadrature to obtain the total error.

The effect of Kan Jang extract on the pharmacokinetics and pharmacodynamics of warfarin in rats.

Significant pharmacokinetic/pharmacodynamic interactions between various herbal products and warfarin have recently been reported. The aim of this study was to determine whether concomitant treatment of rats with Kan Jang (a standardized fixed combination of extracts from Andrographis paniculata and Eleutherococcus senticosus) and warfarin would lead to an alteration in the pharmacological effects of warfarin. Each day for 5 days a group of animals was treated orally with an aqueous solution of Kan Jang at a dose of 17 mg/kg of the active principle andrographolide (a daily dose some 17-fold higher than that recommended for humans): the control group received similar treatment with appropriate volumes of water only. Sixty minutes after the final daily administration of Kan Jang or water, an aqueous solution of warfarin (0.2 mg/ml) was given to each animal at a dose of 2 mg/kg. From each group, 6 animals were sacrificed at 0, 2, 4, 6, 8, 12, 24, 30 and 48 h after warfarin administration and blood samples taken. The concentration of warfarin in blood plasma was measured by capillary electrophoresis using 50 mM borate buffer (pH 9.3) as mobile phase with simultaneous detection of warfarin at 208.1 and 307.5 nm. Prothrombin time in blood plasma was measured using thromboplastin reagent. The concomitant application of Kan Jang and warfarin did not produce significant effects on the pharmacokinetics of warfarin, and practically no effect on its pharmacodynamics.

Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and human.

Validated analytical methods (HPLC, CE and GC-MS) for determining the amount of andrographolide (AND) in the blood plasma of rats and human volunteers following the oral administration of Andrographis paniculata extract (APE) and Andrographis paniculata fixed combination Kan Jang tablets were developed and used for the pharmacokinetic study. Andrographolide was quickly and almost completely absorbed into the blood following the oral administration of APE at a dose of 20 mg/kg body wt. in rats. Its bio-availability, however, decreased four-fold when a 10-times-higher dose was used. Since a large part (55 %) of AND is bound to plasma proteins and only a limited amount can enter the cells, the pharmacokinetics of AND are described well by a one-compartment model. Renal excretion is not the main route for eliminating AND. It is most likely intensely and dose dependently metabolized. Following the oral administration of four Kan Jang tablets (a single therapeutic dose, equal to 20 mg of AND) to humans, maximum plasma levels of approximately 393 ng/ml (approx. 1.12 microM) were reached after 1.5-2 hours, as quantified using a UV diode-array detection method. Half-life and mean residence times were 6.6 and 10.0 hours, respectively. AND pharmacokinetics in humans are explained well by an open two-compartment model. The calculated steady state plasma concentration of AND for multiple doses of Kan Jang (after the normal therapeutic dose regimen, 3 x 4 tablets/day, about 1 mg AND/kg body wt./day) was approximately 660 ng/ml (approx. 1.9 microM), enough to reveal any anti-PAF effect, particularly after drug uptake when the concentration of AND in blood is about 1342 ng/ml (approx. 3.8 microM, while for anti-PAF effect EC50 - 5 microM).