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An asymmetric synthesis method has been suggested as a feasible approach for the preparation of fluorine-18-labeled (T1/2 110 min) analog of l-threo-3,4-dihydroxyphenylserine, i.e., 6-l-threo-[18F]FDOPS ((2S,3R)-2-amino-3-(2-[18F]fluoro-4,5-dihydroxyphenyl)-3-hydroxypropionic acid), a new radiotracer for the evluation of norepinephrine transporters by positron emission tomography (PET). The approach is based on the condensation reaction of 2-[18F]fluoro-4,5-bis(methoxymethoxy)benzaldehyde with a chiral nickel(II) complex and glycine (Ni-(R)-BPB-Gly) with subsequent removal of protection from hydroxy groups by acid hydrolysis. The radiochemical synthesis includes three steps and can be easily implemented into modern automated modules for the synthesis of radiopharmaceutical agents for PET.

A simple direct-coding interpolator with a secured monotonicity of the quantization characteristic of an interpolated time interval at the limiting operation speed of the used circuitry components and with automatic matching of the coarse and precise reading scales at the hardware level is described.

The spectroscopic analysis of composition of highly scattering media, in particular, biological tissues, is associated with difficult interpretation of the spectrum of radiation subjected to both absorption and multiple scattering in a medium. The proposed technique of the combined analysis of spectra of laser radiation fluorescence and diffuse reflection by highly scattering biological media allows quantitative determination of concentrations of basic chromophores and fluorophores in tissues with simultaneous estimation of structural changes in objects under study. To determine the effect of structural parameters on the intensity of backscattered laser and fluorescent radiation, numerical simulation and physical modeling of the interaction of exciting and fluorescent radiation with highly scattering media are performed. The dependences of the measured signal on the concentrations of scatterers and fluorophore (protoporphyrin IX) under study are measured.

Catalytic activity of palladium layers in reduction of atmospheric oxygen and oxidation of methanol and ethanol in an alkaline medium was studied for electrolytic palladium deposits on porous nickel substrates by cyclic voltammetry on a rotating disk electrode.

A series of the anionic CoIII complexes based on optically active amino acids containing the lithium cation in the external sphere of the complex was synthesized. The synthesized compounds were used as catalysts in the asymmetric addition of trimethylsilyl cyanide to aldehydes. The influence of the temperature, catalyst concentration, and modification of the chiral anion structure on the enantioselectivity of catalysis was studied.

Addition of anaferon (pediatric formulation) to the therapy of chickenpox patients led to more rapid disappearance of the main symptoms and alleviated the course of the disease. The safety of the preparation is confirmed by the absence of undesirable events and stability of laboratory indexes against the background of therapy.

O-(2'-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]FET) has gained much attention as a promising amino acid radiotracer for tumor imaging with positron emission tomography (PET) due to favorable imaging characteristics and relatively long half-life of (18)F (110min) allowing remote-site application. Here we present a novel type of chiral enantiomerically pure labeling precursor for [(18)F]FET, based on NiII complex of a Schiff's base of (S)-[N-2-(N'-benzylprolyl)amino]benzophenone (BPB) with alkylated (S)-tyrosine, Ni-(S)-BPB-(S)-Tyr-OCH2CH2X (X=OTs (3a), OMs (3b) and OTf (3c)). A series of compounds 3a-c was synthesized in three steps from commercially available reagents. Non-radioactive FET as a reference was prepared from 3a in a form of (S)-isomer and (R,S) racemic mixture. Radiosynthesis comprised two steps: (1) n.c.a. nucleophilic fluorination of 3a-c (4.5-5.0mg) in the presence of either Kryptofix 2.2.2.or tetrabutylammonium carbonate (TBAC) in MeCN at 80 degrees C for 5min, followed by (2) removal of protective groups by treating with 0.5M HCl (120 degrees C, 5min). The major advantages of this procedure are retention of enantiomeric purity during the (18)F-introduction step and easy simultaneous deprotection of amino and carboxy moieties in 3a-c. Radiochemically pure [(18)F]FET was isolated by semi-preparative HPLC (C18 mu-Bondapak, Waters) eluent aq 0.01M CH(3)COONH(4), pH 4/C(2)H(5)OH 90/10 (v/v). Overall synthesis time operated by Anatech RB 86 laboratory robot was 55min. In a series of compounds 3a-c, tosyl derivative 3a provided highest radiochemical yield (40-45%, corrected for radioactive decay). Enantiomeric purity was 94-95% and 96-97%, correspondingly, for Kryptofix and TBAC assisted fluorinations. The suggested procedure involved minimal number of synthesis steps and suits perfectly for automation in the modern synthesis modules for PET radiopharmaceuticals. Preliminary biodistribution study in experimental model of turpentine-induced aseptic abscess and Glioma35 rat's tumor (homografts) in Wistar rats has demonstrated the enhanced uptake of radiotracer in the tumor area with minimal accumulation in the inflamed tissues.

Chiral, coordinatively-saturated cobaltate(III) complexes of Schiff bases obtained from salicylaldehyde and the optically active amino acids, ( S )-Val, ( S )-Thr, and ( S )-Trp, are formed as C 2 -symmetrical, octahedral, anionic Λ( S , S )-, and Δ( S , S )-diastereoisomeric complexes, which are easily separable by chromatography. The complexes are stereochemically inert and, thus, are not transformed into each other under normal conditions. The counter-cations of the complexes can be easily interchanged and the sodium, potassium, and silver salts of some of the complexes were prepared. The structures of diastereoisomeric Λ-[(Sal-( S )-Val) 2 Co(III)] − Ag + and Δ-[(Sal-( S )-Val) 2 Co(III)] − Ag + were established by single crystal X-ray analysis. All of the sodium and potassium complexes effectively catalyzed the reaction between benzaldehyde and Me 3 SiCN, but only the Λ-[(Sal-( S )-Trp) 2 Co(III)] − K + complex gave rise to enantiomerically-enriched mandelonitrile with up to 77% ee. The silver salts catalyzed a Mukaiyama reaction with low enantioselectivity (ee in the range 6–27%).

A new procedure was suggested for asymmetric synthesis of of 6-[18F]fluoro-3,4-L-dihydroxyphenylalanine (6-18F-L-FDOPA), an important radiotracer for studies of the dopaminergic system by positron emission tomography (PET). The key step of the synthesis is stochiometric asymmetric alkylation of chiral Ni(II) complexes using 3,4-methylenedioxy-6-[18F]fluorobenzyl bromide as alkylating agent. A series of Ni(II) complexes containing various substituents in the benzyl group were tested. The highest enantiomeric purity of 6-18F-L-FDOPA was attained with the complex derived from (S)-N-(2-benzoylphenyl)-1-(3,4-dichlorobenzyl)-pyrrolidine-2-carboxamide, Ni-DCBPB-Gly, under mild alkylation conditions (CH2Cl2, 40°C, potassium tert-butylate as base). Such conditions are favorable from the viewpoint of synthesis automation. The radiochemical yield of 6-18F-L-FDOPA corrected for the radioactive decay was 10–15% at a synthesis time of 120 min, including purification by semipreparative HPLC. The radiochemical and chemical purity of the product exceeded 99%, and the enantiomeric purity was as high as 95%, meeting the requirements for using 6-18F-L-FDOPA in PET practice.

The application of backward diffuse reflection (BDR) spectroscopy for in vivo monitoring the degree of haemoglobin oxygenation and concentration of photosensitisers in tissues subjected to photodynamic therapy is demonstrated. A simple experimental technique is proposed for measuring diffuse reflection spectra. The measurements are made under steady-state conditions using a fibreoptic probe with one transmitting and one receiving fibre separated by a fixed distance. Although this approach does not ensure the separation of contributions of scattering and absorption to the spectra being measured, it can be used for estimating the degree of haemoglobin oxygenation and concentration of photosensitisers in the tissues. Simple expressions for estimating the concentration of photosensitisers from the BDR spectra are presented and the accuracy of this approach is analysed. The results of application of BDR spectroscopy for monitoring various photosensitisers are considered.

Diastereoselective synthesis of new NiII complexes of Schiff bases of (S)-2-[N-(N-benzylprolyl)amino]benzophenone with (2S,4R)-4-bromoglutamic, (1S,2R)- and (1S,2S)-1-aminocyclopropane-1,2-dicarboxylic acid monoesters was performed.

All four diastereomers of 3-(trans-2-nitrocyclopropyl)alanine (3) were prepared by asymmetrically induced α-C alkylation of the glycine moiety in the [(S)- or (R)-Schiff base]NiII complex 7, employing racemic trans-1-(iodomethyl)-2-nitrocyclopropane (8) as the alkylating agent. A notable difference in solubility between the two diastereomeric products 9a/9b [when (S)-7 was used as starting material] or 9d/9e [when (R)-7 was employed] allowed for their separation from the same reaction mixture. All the diastereomers of 3-(trans-2-nitrocyclopropyl)alanine (3) were produced upon brief exposure of the alkylation products 9 to dilute hydrochloric acid, with subsequent purification by ion-exchange chromatography and crystallization. The absolute configurations of the nickel complexes 9a−e were established by X-ray crystallographic analyses. In addition, the X-ray crystal structure of (2S,1′S,2′R)-3 was determined to confirm the convergence of the configurations of the parent nickel complexes 9 with those of the amino acids 3 derived from them. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Clinical studies have revealed high selectivity of 5-ALA-induced protoporphyrin IX accumulation in different brain tumors. Modern methods of evaluation of tissues visible fluorescence are based on the qualitative analysis of the images. Up-to-date methods of combined spectral analysis allow fulfilling the intraoperative quantitative evaluation of the protoporphyrin IX content, as well as the scattering and absorption properties of a tissue. This paper presents a new method of the simultaneous analysis of hemoglobin concentration in oxygenated and reduced forms, tumor marker concentration (5-ALA-induced PP IX) and a new way to analyze the changes in the scattering properties of the tissues. The method is implemented by splitting the visible spectrum into intervals where hemoglobin and protoporphyrin IX have the characteristic peaks of absorption and fluorescence. The present method shows the dependence of the fluorescence index from the tumor grade. Combined spectroscopy (optical biopsy) can detect the differences between the subtypes of gliomas that are similar in the protoporphyrin IX fluorescence index. This method complements and enhances the diagnostic capabilities of spectroscopy, which is particularly important in the non-fluorescent glioma surgery.

Alkali metal salts of substituted (S)-prolines, alkali metal alkoxides of (S)-prolinol, and Na salts of chiral substituted 2-amino-2"-hydroxy-1,1"-binaphthyls can catalyze the asymmetric Michael reaction of diethyl malonate with crotonaldehyde to give adducts in >90% yields with ee up to 40%. The influences of the catalyst structure, the nature of the alkali metal cation, temperature, the solvent, and salt additives on the reaction outcome were studied.

Data on the electrochemical oxidation of a model phenol solution (100 mg/l) in the presence of sodium chloride (10 g/l) are presented. It is shown that active chlorine yielded by the electrolysis is directly involved in the electrochemical oxidation of phenol, which proceeds with destruction of the aromatic ring. In the course of the oxidation of the model phenol solution on Pt/Pt, under the conditions of electrochemical generation of active chlorine, no dioxine structures form.

Preparative syntheses of enantiopure (S)- and (R)-Dip by α-C-alkylation with Ph2CHX (X=Cl or Br) of the glycine moiety in a Ni(II) Schiff's base complex 1 derived from glycine and (S)- or (R)-[(N-benzylprolyl)amino]benzophenone (BPB) is described. The diastereoselectivity of the alkylation with PhCH2Br in DMF in the presence of NaOH is both kinetically and thermodynamically controlled.

To evaluate a role of dopamine transmission in the theory of mind (ToM) dysfunction in schizophrenia, authors studied the association of ToM with COMT and DRD2 gene polymorphisms in 209 patients with schizophrenia and 172 healthy people. All subjects performed second-order false belief (FB2) and faux pas stories. The association between the COMT Val158Met polymorphism and performance on FB2 was found. The association was sex-specific. The worse performance was associated with a Met allele in female patients and with the ValVal genotype in male ones. A correlation analysis of the COMT Val158Met polymorphism, performance on FB2 task, neurocognitive and clinical symptoms suggests that in female patients the association was modified, in part, by the higher stress sensitivity caused by the severity of clinical symptoms and its consequences for cognitive functioning.

Growing evidence suggest that interleukin-1beta (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) are involved in the pathogenesis of schizophrenia. The objective of this study was to test the association of the functional promoter polymorphism 511TC of the IL-1B gene and the VNTR polymorphism of the IL-1RN gene with clinical symptoms of schizophrenia. We studied 758 patients, 415 men and 343 women, with the ICD-10 diagnosis of schizophrenia. Symptoms of schizophrenia were measured using the Positive and Negative Symptome Scale (PANSS). The sample was stratified by gender and type of schizophrenia (chronic or episodic). We found the association between the VNTR IL-1RN polymorphism and PANSS negative symptoms (p = 0.02) in men. Male patients with the genotype 2*2 had lower scores than those with 1*2 and 1*1 genotypes. The genotype 2*2 was associated with a more severe illness course (shorter illness duration and smaller number of hospitalizations) as well. The results suggest that the VNTR polymorphism in the IL-1RN gene may be a predictor of outcome of schizophrenia in men.

Different techniques are used today in neurosurgery for intraoperative navigation, including metabolic guidance using 5-aminolevulinic acid (5-ALA). The article focuses on history of intraoperative photodynamic diagnosis (PDD), mechanisms of 5-ALA action, possibilities of its application in different areas of neurosurgery. In addition to visual assessment of fluorescence, laser biospectroscopy significantly increases the diagnostic value of PDD. Laser biospectroanalysis is described in details, wide perspectives of its application in neurosurgery are demonstrated.

Regioselectivity and diastereoselectivity of the addition of BrCCl3 to (R)-3-(E)-cinnamoyl-4-phenyloxazolidin-2-one (1) and (R)-3-(E)-acryloyl-4-phenyloxazolidin-2-one (2) catalyzed by Fe(CO)5 or initiated with benzoyl peroxide were investigated. Stereochemistry of the reaction of BrCCl3 with the a-complexes (4R,αS,βS)-ν2-(3-(E)-cinnamoyl-4-phenyl-oxazolidin-2-one)irontetracarbonyl (3a) and (4R,αR)-η2-(3-acryloyl-4-phenyloxazolidin-2-one)irontetracarbonyl (4b) was also studied. The results obtained allow the following conclusions to be drawn: (1) the thermal Kharasch reaction catalyzed by Fe(CO)5 proceeds by a redox catalysis mechanism; (2) iron (in any of its oxidation states) is not coordinated to olefins in the transition state of the reaction; (3) the transfer of the halogen atom on the radical adduct probably occurs inside a radical-iron cation pair.

The enzyme (lipases and chymotrypsin)-catalyzed hydrolysis of Schiff bases derived from racemic amino acid esters and aromatic aldehydes has been investigated. The reactions were successfully carried out in different aqueous organic solvents at ambient temperature, but the aqueous acetonitrile (5.4% water content by volume) was the solvent of choice. The l-amino acid (ee 98%) precipitated out from the solution as the reaction progressed, and the liberated aldehyde and unhydrolyzed d-ester (ee 40−98%) remained in the solution. The range of substrates included amino acids having different types of side chains. The addition of an organic base (DABCO) into the solution resulted in the racemization of the remaining d-ester and the additional hydrolysis of the substrate, thus leading to the effective asymmetric transformation of the initial ester. Upto 87.5% of the initial racemate was converted into the l-enantiomer.

Absence of well-defined borders of the glial tumor due to their infiltrative growth is one of the main issues in neurosurgery. A number of methods for intraoperative visualization are available today. The fluorescent metabolic navigation with 5-aminolevulinic acid (5-ALA) combined with quantitative laser spectroscopy is one of the latest technique. In our series of 99 consecutive patients with brain gliomas (WHO Grade I-IV) we found that visible fluorescence was observed in 68% of cases. Additional use of the laser spectroscopy could increase method sensitivity up to 74% due to accumulation of the protoporphyrine IX in nonfluorescense tumors. It was shown that there are some differences in quantitative fluorescence not only within same tumor (glioblastoma) but also in-between low- and high-grade gliomas. Intraoperative fluorescence and laser spectroscopy are effective and very helpful methods of intraoperative imaging in of intrinsic brain tumor surgery.

Photodynamic diagnosis (PDD) has been actively implemented into neurooncological practice, especially in cerebral gliomas surgery. This paper describes our first experience of PDD combined with laser spectroanalysis in intracranial meningiomas. The study included 21 patients (8 male and 13 female patients, mean age was 58 years, range--between 37 and 74 years) with intracranial meningiomas operated with PDD in Burdenko Neurosurgical Institute between 2008 and 2011. In 14 cases laser spectroanalysis was used. Tumor fluorescence was present in all but one cases (95%). Spectroanalysis demonstrated that peaks of fluorescence varied between 5 and 46 (mean level was 18.5). These data correlated with visual impression of fluorescence and confirmed that meningioma is a tumor with bright fluorescence. Radical removal (Simpson grade I-II) was achieved in 10 cases, subtotal resection was performed in the rest of the patients. Application of PDD and laser spectroanalysis allows gaining complete information about accumulation of photosensibilizer in the tissue. To our opinion, these methods may be the most useful for determination of the borders of dural and bony invasion which directly affects the surgical tactics and degree of radical removal. Further studies are needed to evaluate the influence of PDD and laser spectroanalysis on long-term surgical outcomes.

Alkali metal salts of substituted (S)-prolines, alkali metal alkoxides of (S)-prolinol, and Na salts of chiral substituted 2-amino-2"-hydroxy-1,1"-binaphthyls can catalyze the asymmetric Michael reaction of diethyl malonate with crotonaldehyde to give adducts in >90% yields with ee up to 40%. The influences of the catalyst structure, the nature of the alkali metal cation, temperature, the solvent, and salt additives on the reaction outcome were studied.

The authors elucidate an experience with using multislice spiral computed tomography with the method of multiphase scanning (CT-angiography) in patients with suspected tumors of organs of the biliopancreatoduodenal zone. The proposed method allows getting information on the character of the pathological process, dissemination of the tumor lesion. It helps to decide on the strategy of treatment of the patient, to plan the operative intervention and assess the results of operative treatment.

We propose a method for the synthesis of aspartic and α-methylaspartic acids by alkylation with ethyl bromoacetate of the α-carbon atom of the amino acid moiety in Ni(II) complexes of Schiff bases of glycine with (S)-2-[(N-benzylprolyl)amino]benzophenone and alanine with (S)-2-[(N-benzylprolyl)amino]-benzaldehyde, respectively. Attempts to synthesize α-methylaspartic acid by oxidative cleavage of the C=C bond to a COOH group in the complex of the Schiff base of α-allylalanine with (S)-2-[(N-benzylprolyl)amino]benzophenone were unsuccessful.

The kinetic and thermodynamic diastereoselectivity of the hydroxymethylation of the alanine fragment in the Ni(II) complex of the Schiff base of alanine and (S)-2-[(N-benzylprolyl)amino]benzophenone (BBP) was studied. Optically pure (R)- and (S)-α-methylserines were synthesized.

The labyrinthine zone of allantoic placenta was studied after dosated exposure to vibration. The study was carried out in pregnant female Wistar rats (n=68). Rats were subjected to short-term vibration from Day 9 to Day 13 and long-term vibration from the Day 9 to Day 18 of pregnancy (taking into account embryogenesis periodization and the development period of extraembryonic organs). Vibration table with fixed parameters (frequency of 32 Hz and acceleration of 50 m/s2) was used. Placental and fetal mass were measured, labyrinthine zone components were evaluated using the morphometric methods, while labyrinthine cord and fetal vessels along Duval's sinus were studied ultrastructurally. Labyrinth was analyzed from the point of view of rapprochement of maternal and fetal bloodstreams. It was found that the exposure to vibration together with the development of compensatory adaptive mechanisms led to chronic placental insufficiency. Experimental group with short-term vibration exposure (Days 9-13) is of particular interest since chronic placental insufficiency in this group should be considered as decompensated.

Chiral coordinatively saturated cobalt(III) complexes with Schiff bases of enantio-pure amino acids are formed as Λ and Δ-isomers, which are not transformed into each other under normal conditions. These complexes catalyze the formation of enantiomerically enriched cyanohydrins from aldehydes and Me3SiCN under homo-and heterogeneous catalysis.

The shore of Lake Aral in Kazakhstan is a perfect area for studying the human adaptation strategy to past climate changes. New archaeological material, gathered along the northern shores during the expedition of the INTAS project 'CLIMAN', is briefly presented. Changes in settlement activity during the Atlantic and Subboreal are related to lake level changes of the Aral Sea. A previ-ously proposed lake level maximum needs to be revised. In particular the lake level stand at 72/73 m, with an assumed age of 5000 BP is definitely refused. Based on the presented data the maximum lake level most probably never reached beyond 57/58 mean average sea level (masl). Furthermore the regression during the 15th–16th centuries has been underestimated. It may have been lower than the present day level. Thus the present desiccation of the Aral Sea is historically not unique, as a similar regression, probably induced by man as well, has occurred at least once during history. A readjustment of the water level is, therefore, possible at any time.

The Wittig—Horner reaction of CbzNHCH(CO2Me)P(O)(OMe)2 (1) with ArCHO (2) in the presence of Et3N as a base affords methyl (Z)-3-aryl-2-(carbobenzoxyamino)acrylates (3) with high degrees of diastereoselectivity (Z)/(E) > 10∶∶1. One recrystallization of the crude product is sufficient to obtain isomerically and chemically pure (Z)-3.

Tolerance of physical load was investigated in 50 convalescents of hemorrhagic fever with renal syndrome (HFRS) at bicycle exercise test (BET). Calculations were made of maximal oxygen consumption and energy consumption at the threshold load. It is shown that for three months after HFRS physical performance of the convalescents remained low. By the end of the expected disability objective recovery of physical performance was registered only in 33-37% convalescents. More than for 3 months disability persisted in reconvalescents engaged in professions with energy consumption above 4.1 kkal/min throughout the working day. Use of BET in the practice of medical labour expertise of HFRS convalescents provides an objective assessment of their working ability and feasible job.

Hyperbaric oxygenation (HBO) was added to the complex of intensive care for 14 full-term newborns born asphyxiated and with cerebral circulation disorders of the I-II degree. Study of the antioxidant enzymatic system and free-radical oxidation by chemiluminescence showed no changes in superoxide dismutase and catalase and a 1.6-2 times increase in the activity of glutathione peroxidase, on the one hand, and an appreciable decrease of free radical processes, on the other. This permitted a conclusion about the absence of toxic effects during HBO and on its membrane-stabilizing action.

Is is established that saturation of a Fe78B12Si9Ni1 amorphous alloy ribbon with hydrogen leads to a several-fold increase in the emf observed under the Barkhausen effect conditions. The magnitude of the observed effect is related to the hydrogen content in the alloy.

1. The presence of a neighboring valine fragment in the potassium Λ- and Δ-[N-salicylideneglycinato-N-salicylidene-S-valinato] cobaltates (III), compounds (I) and (II), reduces the CH-acidity of the glycine fragment, and the rate of C-C bond formation, as compared with sodium bis[N-salicylideneglycinato]cobaltate(III). 2. The chiral center of the valine fragments of (I) and (II) exerts a stereochemical effect on the kinetics and thermodynamic steroselectivity of C-C bond formation between the complexes valine fragments and the acetaldehyde.

Water-soluble polyacrylamide samples of various molecular weight, containing salicylaldehyde and lysine moieties, were prepared by copolymerization of (Nα-5-methacryloylamino-salicylidene-Nϵ-methacryloyl-(S)-lysinato) (pyridine)copper (II) (1) with acrylamide, followed by destruction of the copper complex by the disodium salt of EDTA. It is shown that at pH > 6 the formation of “internal” aldimine occurs in these samples. The degree of assembly of “internal” Schiff base is considerably higher than in the model low-molecular weight system and does not depend on: a) the molecular weight of the polyacrylamide sample; b) the polymer concentration in buffer solution; c) the presence of a cross-linking agent. On the basis of these data a conclusion is made that in the copolymerization of 1 with acrylamide, methacryloyl moieties, bonded with the amino groups of salicylaldehyde and lysine, form macrocycles, the cyclocopolymerization rate being much higher than the rate of cross-linked polymer formation. After the removal of copper ions from the polymer the lysine and salicylaldehyde moieties remain attached to the same polymer chain in the immediate vicinity of each other, thus favouring the formation of “internal” aldimine.