In Vitro Modeling of Co-Transplantation of Multipotent Stromal Mesenchymal Cells from Orbital Fat Pad and Lipoaspirate of Human Subcutaneous Adipose Tissue in Organ Culture in Collagen Gel.

The interplay of multipotent stromal cells derived from the orbital fat pads and cells of the lipoaspirate from the subcutaneous adipose tissue was studied using in vitro co-transplantation model in an organ culture in a collagen gel. Microscopy findings and intensity of apoptosis and cell proliferation in cultures of lipoaspirate with and without multipotent stromal cells showed that the cells maintained their viability, proliferation capacity, and cytokine secretion activity. Higher proliferatitive activity of cells in cocultures promotes renewal of fat transplant cells and can help to maintain its stable volume in delayed terms after transplantation.

[Screening of potential antibiotics, inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis--2-C-methyl-D-erythritol-2,4-cyclodiphosphate derivatives].

The recently discovered nonmevalonate pathway of isoprenoid biosynthesis is a prospective target in screening of new antibiotics. Because of the absence of the pathway in the animal cells, the specific inhibitors of the pathway will be a new class of antibiotics against many pathogens (which cause, e.g., malaria, tuberculosis, etc), combining high efficiency and low toxicity. Several derivatives of 2-C-methyl-D-erythritol-2,4-cyclodiphosphate (MEC) were synthesized. 4-Phospho-methyl-D-erythritol-1,2-cyclophosphate, benzyl ether and benzyliden derivative of MEC inhibited the 14C-MEC incorporation into isoprenoids of chromoplasts from red pepper with IC50 of 1.7-5 MM. Some inhibition (about 10%) was also observed with the use of dimethyl ether and isopropyliden derivative of MEC.

[Physical adaptability of the cardiorespiratory complex in sailors of European North].

The authors assessed physiological adaptation in 26 divers and 54 submariners doing military service in the Arctic circle of the European North. There was a stable regulation of cardiac rhythm due to its vasomotor component in the divers and autonomic lability in the submariners, a worse reaction to orthostatic changes during functional tests in the divers than in the submariners. The orthostatic test-induced reduction in the total power of the cardiac rhythm variability spectrum in the submariners was referred by the authors to as the asthenic phenomena caused by the specificity of their service activities. The distinctive type of divers' respiration, which was characterized by lower velocity properties and ample possibilities during forced respiration, was detected.

[2-(14)C-Methylerythritol 2,4-cyclodiphosphate incorporation into bacterial and plant isoprenoids].

To work out a test system for studying the inhibition of isoprenoid biosynthesis through non-mevalonate pathway, the conversion of 2-(14)C-methylerythritol 2,4-cyclodiphosphate (14C-MEC) into isoprenoids of three bacteria species and into plastids of 11 higher plant species was studied. The highest efficiency (up to 63%) of the process was observed with chromoplasts from narcissus (Narcissus pseudonarcissus L.) and celandine (Chelidonium majus L.). Twenty five percent of added 14C-MEC was recovered in an isoprenoid fraction of red pepper (Capsicum annuum L.) chromoplasts. Thus, these three models can be used to test antibiotic inhibitors of isoprenoid biosynthesis.

[Adaptation of divers in the European North].

The article gives a value of physiological condition of plungers's organisme during the most unfavorable season of the year-- polar night--in condition of based planed readiness (n = 26). Data of researches concluded necessary parameters of anthropometry, homodynamic, respirator functions. Supplementary diagnostic base was made by methods from the program of express-control of functional conditions. The results of the searches gave an opportunity to esteem the examined group of service men as people with tight vegetal nervous system, high level of neurohumoral regularity, which common for the physically strong people. It confirms the effectiveness of existing system of choice of plungers. The authors offer to fix a system of physiological monitoring of the health of all the service men. The purpose of this action is an early revelation of donozoologial conditions.

[Interrelation between the pathways of isoprenoid biosynthesis and carbon source catabolism in anaerobic and facultatively anaerobic bacteria].

Data on the interrelation between the pathways of the carbon source catabolism and isoprenoid biosynthesis in anaerobic and facultatively anaerobic bacteria were obtained. Two pathways of isoprenoid biosynthesis (nonmevalonate and mevalonate) were revealed in the representatives of the genus Clostridium. The non-mevalonate pathway of isoprenoid biosynthesis and the glycolytic pathway of substrate oxidation are typical of glucose-grown bacteria, whereas the pentose phosphate cycle operates in xylose-grown bacteria. The mevalonate pathway of isoprenoid biosynthesis was revealed in strain Clostridium thermosaccharolyticum DSM 571 grown in the presence of mevinolin, as well as in a number of lactic acid bacteria. Mevinolin is known to react with the lactate dehydrogenase complex, preventing reduction of pyruvate. The nonmevalonate pathway of isoprenoid biosynthesis was revealed in Bifidobacterium bifidum. The role of different metabolic pathways in isoprenoid biosynthesis is discussed.

[The role of 2-C-methylerythritol-2,4-cyclopyrophosphate in the resuscitation of the "nonculturable" forms of Mycobacterium smegmatis].

2-C-Methyl-D-erythritol-2,4-cyclopyrophosphate (MEC), an intermediate of the biosynthesis of isoprenoid compounds in bacteria, was found to be capable of exerting a resuscitating effect on resting Mycobacterium smegmatis cells. The introduction of an additional copy of the ispE gene encoding cytidyl-methylerythritol kinase, an enzyme involved in MEC synthesis in M. smegmatis, resulted in the emergence of a capacity for spontaneous reactivation of "nonculturable" M. smegmatis cells, which is not characteristic of the wild-type cells of this species. The involvement of MEC in the transition from the "nonculturable" state to the state of active growth is indicative of a previously unknown function of MEC, assumed to consist in regulation of the bacterial genome activity.

[Evaluation of in vitro antibacterial activity of fosmidomycin and its derivatives].

Unlike the mammals, some species of pathogenic microorganisms synthesize isoprenoids by the mevalonate-independent pathway known as the methyl-erythritol phosphate pathway (MEP). The macromolecules of the polyprenyl compounds play an essential role in the metabolism of the microbial cell. Therefore, the MEP enzymes can be targets for new antibiotics. Antibacterial activity of fosmidomycin, an inhibitor of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), the key enzyme of MEP in isoprenoid biosynthesis was estimated. By the results of the in vitro experiments the tested microorganisms were divided into susceptible and resistant to fosmidomycin. Vaccinal strains of B. anthracis and practically all the strains of P. aeruginosa were included into the first group. The minimum inhibitory concentrations of fosmidomycin for them determined by the method of serial dilutions were 1-8 mcg/ml. The second group for which the MICs were 16-64 mcg/ml included representatives of Listeria, Yersinia and Burkholderia. The tested species of enteric bacteria, Mycobacterium, Corynebacterium, Campylobacterium and the tularemia vaccinal strain were fosmidomycin resistant. The MICs for them varied from 128 to 512 mcg/ml. Since all the above mentioned bacteria have DXR, resistance to fosmidomycin was conjectured with the difficulty of its delivery to the target in the microbial cell. To increase penetrability of fosmidomycin, various functional groups modifing its hydrophoby were added to the antibiotic molecule. However, no expected increase of the susceptibility to the derivatives was achieved probably because their affinity to DXR lowered. Penetrability of fosmidomycin to the cell was facilitated by using its combinations with compounds influencing the integrity of the bacterial cell membrane. Combined use of fosmidomycin with polymyxin B, chlorhexidine and cetrimide 4-64 times lowered its MICs for the strains of Listeria, Burkholderia and Yersinia.

[Isoprenoid pigments in representatives of the family Microbacteriaceae].

By using fosmidomycin and mevinolin (inhibitors of the synthesis of isoprenoid pigments), spectrophotometry, and mass spectrometry, the presence of isoprenoid pigments is shown in 71 of the 78 strains under study. All of these strains belong to 11 genera of the family Microbacteriaceae. Yellow, orange, and red pigments are found to have absorption spectra typical of C40-carotenoids. Eight out of the sixteen strains of the genus Microbacterium are able to synthesize neurosporene, a precursor of lycopene and beta-carotene. The biosynthesis of carotenoids in some representatives of the genera Agromyces, Leifsonia, and Microbacterium is induced by light. Inhibition of the biosynthesis of isoprenoid pigments by fosmidomycin suggests that they are synthesized via the nonmevalonate pathway. Twelve strains are found to exhibit both the nonmevalonate and mevalonate pathways of isoprenoid synthesis. These data, together with the difference in the inhibitory concentration of fosmidomycin, can be used for differentiating various taxa within the family Microbacteriaceae.

[Prevalence of nonmevalonate and mevalonate pathways for isoprenoid biosynthesis among bacteria of different systematic groups].

The effect of fosmidomycin and mevinoline, inhibitors of the nonmevalonate and the mevalonate pathway of isoprenoid biosynthesis, respectively, on the growth of 34 anaerobic and 10 aerobic prokaryotic strains was studied. Fosmidomycin at the concentrations used was shown to inhibit the growth of 9 (of 10) representatives of the family Microbacteriaceae, 4 (of 5) strains of Thermoanaerobacter, and 11 (of 12) strains of Clostridium, whereas mevinoline inhibited the growth of lactobacilli (Carnobacterium), methanogenic and sulfate-reducing bacteria insensitive to fosmidomycin. During the late growth phase, four strains of actinobacteria (of nine) accumulate the compound, which, upon oxidation, generates a long-lived free radical; three strains synthesize 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEC). It was concluded that the difference in the sensitivity of the organisms to fosmidomycin and mevinoline might serve as a test to differentiate several representatives of the family Microbacteriaceae. The use of mevinoline for inhibiting methanogens in ecological investigations seems to be promising.

Eu3+ coordination in an organic/inorganic hybrid matrix with methyl end-capped short polyether chains.

Fourier Transform mid-infrared (FT-IR), Fourier Transform Raman (FT-Raman) and photoluminescence spectroscopies and Two-Dimensional (2D) Correlation Spectroscopic Analysis were employed to examine the anionic and cationic local environments in mono-urethanesils doped with europium triflate (Eu(CF(3)SO(3))(3)). The hybrid host framework of these materials is composed of a siliceous backbone bonded through urethane linkages to CH(3)-terminated polymer chains containing about 7 OCH(2)CH(2) units. Samples with infinity >/= n (composition) >/=5 (where n = OCH(2)CH(2)/Eu(3+)) were studied. In terms of ionic association, the level of complexity of these xerogels is very high. In all the compounds the triflate ions exist "free", weakly coordinated and forming cross-link separated ion pairs. At 20 >/= n >/= 5, in addition to all these species contact ion pairs occur. In agreement with these conclusions, photoluminescence establishes the presence of three distinct cation local sites (Eu(3+)/O=C(urethane cross-links), Eu(3+)/O-C-C(polyether chains) and weakly coordinated Eu(3+)/CF(3)SO(3)(-) ionic pairs).

Local structure and near-infrared emission features of neodymium-based amine functionalized organic/inorganic hybrids.

Nd(3+)-based organic/inorganic hybrids have potential application in the field of integrated optics. Attractive sol-gel derived di-urea and di-urethane cross-linked poly(oxyethylene) (POE)/siloxane hybrids (di-ureasils and di-urethanesils, respectively) doped with neodymium triflate (Nd(CF(3)SO(3))(3)) were examined by Fourier transform mid-infrared (FT-IR), Raman (FT-Raman), (29)Si magic-angle spinning (MAS) nuclear magnetic resonance (NMR) and photoluminescence spectroscopies, and small-angle X-ray scattering (SAXS). The goals of this work were to determine which cation coordinating site of the host matrix (ether oxygen atoms or carbonyl oxygen atoms) is active in each of the materials analyzed, its influence on the nanostructure of the samples and its relation with the photoluminescence properties. The main conclusion derived from this study is that the hydrogen-bonded associations formed throughout the materials play a major role in the hybrids nanostructure and photoluminescence properties.

[Free radicals in mercury-resistant bacteria indicate a novel metabolic pathway]. / Svobodnye radikaly u rtut'-rezistentnykh bakterii kak indikatory novogo metabolicheskogo puti.

A mercury resistant-soil bacterium P.10.15, identified as a close relative of Pseudomonas veronii, was shown to accumulate a specific compound in the stationary phase of growth. This compound is converted to a long-lived free radical under oxidizing conditions, as registered by its EPR signal at room temperature. The compound was purified by ion-exchange and gel-filtration chromatography and identified by mass spectroscopy, 2D NMR, and EPR as a trisaccharide beta-D-GlcpNOH,CH3-(1-->6)-alpha-D-Glcp-(1-->1)-alpha-D-Glcp, or, in other words, as 6-O-(2-deoxy-2-[N-methyl]hydroxylamino-beta-D- glucopyranosyl)-alpha-alpha-trehalose, previously discovered in Micrococcus luteus (lysodeikticus) and named lysodektose. The compound is suggested to be a novel intermediate of a previously unknown basic metabolic pathway of trehalose transformation in bacteria, a potential target for antibacterial drug development.

[Properties of 2-C-methyl-D-erythritol 2,4-cyclopyrophosphate--an intermediate in the non-mevalonate isoprenoid biosynthesis]. / Nekotorye svoistva 2-C-metil-D-éritritol-2,4-tsiklopirofosfata--intermediata bezmevalonatnogo puti biosinteza izoprenoidov.

Extraction and purification from the biomass of Corynebacterium ammoniagenes of 2-C-methyl-D-erhythritol 2,4-cyclopyrophosphate (MEC) was associated with its spontaneous transformation into a number of derivatives (which was due to pyrophosphate bond lability and the formation of complexes with metals). These derivatives included 1,2-cyclophospho-4-phosphate, 2,4-diphosphate, 2,3-cyclophosphate, 1,4-diphosphate, and 3,5-diphosphate (identified by 1H, 31P, and 13C NMR spectroscopy) and accounted for about 10% MEC. When added to a solution of DNA in the presence of the Fenton reagent, MEC prevented DNA decomposition. In addition, MEC slowed down the interaction of the reagent with tempol radicals, which indicates that complexation of ferrous ions by MEC attenuates their ability to catalyze the formation of hydroxyl radicals from hydrogen peroxide. In the presence of 0.23 mM MEC, the rate of respiration of rat liver mitochondria increased 1.8 times. At 0.1-1.0 mM, MEC activated in vitro proliferation of human Vgamma9 T-cells. It is suggested that MEC acts as an endogenous stabilizing agent for bacterial cells subjected to oxidative stress and as an immunomodulator for eukaryotic hosts.

[Effect of fosfidomycin on development of various infections in mice]. / Deistvie fosmidomitsina na razvitie nekotorykh infektsii u myshei.

Antibiotic fosmidomycin will know as inhibitor of the nonmevalonate pathway of isoprenoid biosynthesis and as possible antimalarial drug, was shown to possess a certain protective effect on mice experimentally infected with tularemia, tiphus or coli-septicemia. Positive effect on mice with chronic form of tuberculosis was not observed when the animals were given 1 mg of fosmidomycin per capita twice a day. Under oxidative conditions an ESR signal of long living nitroxil free radicals were registered in the water solution of fosmidomycin. The radicals are supposed to be involved in the therapeutic effect of the antibiotic.

[Immunomodulatory properties of 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate and search for its new derivatives]. / Immunomoduliatornye svoistva i poisk novykh proizvodnykh 2-C-Metil-D-éritriol-2,4-tsiklopirofosfata.

A strong immunomodulatory effect of 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEC) responsible for the survival of bacteria was shown on isolated macrophages and in experimental infections in mice (typhoid and tularemia). Derivatives of MEC were found by 1H-NMR spectroscopy under stress conditions in colorless mutants of the bacteria and isolated to be subsequently purified and used for modulation of the immune system of animals.

[An HIV prevalence study by means of sentinel epidemiological surveillance among injection narcotic abusers in Saint Petersburg]. / Izuchenie rasprostranennosti VICh metodom dozornogo épidnadzora sredi potrebitelei in''ektsionnykh narkotikov v Sankt-Peterburge.

The data on the study of the spread of HIV infection among injecting drug users in St. Petersburg, carried out by the method of the random testing of blood remaining in used syringes, are presented. Injecting drug users visiting buses working in accordance with the program "Buses for Assistance to Drug Addicts" were chosen as a study group. The exchange of syringes was one of the elements of this program. The work was carried out in two areas with a high concentration of drug users. The eluates from syringes used by 300 persons were studied. The average rate of the spread of HIV in the cohort under study was 12%. The results were indicative of a high degree of the spread of HIV among injecting drug users in St. Petersburg. Epidemiological patrol surveillance proved to be an effective method for the evaluation of the epidemiological situation in a highly inaccessible group of the population.

[A strategy for the control of HIV infection and viral hepatitides against the background of the narcotic abuse epidemic]. / Strategiia bor'by s VICh-infektsiei i virusnymi gepatitami na fone épidemii narkomanii.

The presence of the epidemic of drug addiction in the Russian Federation is stated: for the recent 10 years the number of drug addicts increased 3.5-fold. The questioning of several thousand drug addicts has revealed that 60% of them have hepatitis B, 80% have hepatitis C, 10% have syphilis. The strategy of controlling HIV infection among drug addicts is proposed. It includes, in the first place, the prevention of the secondary infection from HIV-infected addicts; in the second place, the detection of HIV-infected persons in groups of drug addicts, difficult to establish contacts with; in the third place, the primary prophylaxis within the program "Harm reduction" in the most susceptible groups of drug addicts. The thesis that the prevention of HIV infection must become the prevention of drug addiction by rendering multi-stage assistance to HIV-infected persons, including mainly drug addicts, is substantiated.

[Interaction of bacteria with mercuric compounds]. / Vzaimodeistvie bakterii s rtutnymi soedineniiami.

We investigated the interaction of mercuric compounds with the bacteria Corynebacterium ammoniagenes, Micrococcus luteus, and Mycobacterium smegmatus capable of producing hydroxylamines (R-NOH) and 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MECP), which are prone to form free radicals. The interaction of these substances with Hg2+ ions and their dynamics during the mercuric poisoning of bacteria was studied by EPR and NMR. Under stress conditions induced by lowering pH or generation of active oxygen species, the bacteria and, especially, their mutants with enhanced sensitivity to oxidative stress, were found to respond to exposure to 1-3 micrograms/ml HgCl2 and p-chloromercuribenzoate by a several-fold increase in their viability. The data obtained were interpreted in terms of the involvement of the sulfhydryl groups of bacterial surface proteins in this phenomenon. The interaction of bacteria with mercuric compounds may affect the pathogenesis of tuberculosis and other diseases.