Search

Glycosphingolipids (GSL) are functionally important components of the cell membrane and recognition of their glycan "head" by the immune system is a key part of normal and pathological processes. Recognition of glycolipid antigens on a living cell, their structure, "context" (microenvironment and clustering), presentation including orientation and distance from the plasma membrane, as well as molecular dynamics are important. GSL antigens are targets for the development of anticancer vaccines and therapeutic antibodies, therefore, control of the presentation of their glycans by synthetic methods opens up new possibilities in medicine. In this work, we synthesized 13 GSL analogues as function-spacer-lipids (FSLs) with the same head (blood group A tetrasaccharide, ABO system) but each either differing in the structure of the lipid tail, or the length of the region between the head and the tail, or cluster organization of the head (from 2 to 4 tetrasaccharides in a cluster). The insertion of these FSLs into an artificial and erythrocyte membranes was compared, and their interaction with antibodies was studied, including erythrocyte agglutination. The results give further insight into knowledge of the membrane presentation of GSLs (some results can be extrapolated to glycoproteins) and factors involved in their interaction with antibodies., (© 2024 Wiley-VCH GmbH.)

The high specificity of human antibodies to blood group A and B antigens is impressive, especially when considering the structural difference between these antigens (tetrasaccharides) is a NHAc versus a hydroxyl group on the terminal monosaccharide residue. It is well established that in addition to anti-A and anti-B there is a third antibody, anti-A,B capable of recognizing both A and B antigens. To analyze this AB specificity, we synthesized a tetrasaccharide, where the NHAc of the A antigen was replaced with an NH 2 . This NH 2 group was then used to attach the glycan to an affinity resin, creating an AB epitope (AB ep ) adsorbent where the critical site for recognition by A and B antibodies was not accessible, while the rest of the (conformationally compact) tetrasaccharide remained accessible. Anti-AB ep antibodies were then isolated from blood group O donors and found to have expected A,B specificity against immobilized and red cell bound synthetic antigens, including AB ep , and were able to agglutinate both A and B red cells. The amount of these anti-AB ep (anti-A,B) antibodies found in the blood of group O donors was comparable to levels of anti-A and anti-B found in group B and A individuals. Using STD-NMR the location for the AB epitope on the tetrasaccharide was found., (© 2024 Wiley-VCH GmbH.)

A simple technique for observing optically stimulated electron paramagnetic resonance (OSEPR) is proposed and investigated. The versatility and information content of the described technique is demonstrated by the example of the OSEPR spectra of systems that are unpopular for this type of spectroscopy: a crystal with rare-earth ions Nd 3+ and a doped semiconductor GaAs. In addition, the OSEPR spectrum of atomic cesium is presented, in which an optical nonlinearity is observed that makes it possible to estimate the Rabi frequency for the relevant optical transition. The effects observed in the described experiments (switching of peaks to dips, light-induced splitting of the OSEPR lines, and the appearance of a spectral feature at the double-Larmor frequency) are interpreted using the model proposed in the theoretical part of the work. The suggested interpretation shows the possibility of using the described OSEPR technique to estimate not only 'magnetic' parameters of the model Hamiltonian (g-factors, spin relaxation times), but also the Rabi frequencies characterizing optical transitions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

It is known that linear birefringence of the medium essentially hinders measuring the Faraday effect. For this reason, optically anisotropic materials have never been considered as objects of the Faraday-rotation-based spin noise spectroscopy. We show, both theoretically and experimentally, that strong optical anisotropy that may badly suppress the regular Faraday rotation of the medium, practically does not affect the measurement of the spatially uncorrelated spin fluctuations. We also show that the birefringent media provide additional opportunity to measure spatial spin correlations. Results of the experimental measurements of the spin-noise spectra performed on Nd^{3+} ions in the uniaxial crystal matrices well agree with the theory.

The Southern Ocean surrounding Antarctica is a region that is key to a range of climatic and oceanographic processes with worldwide effects, and is characterised by high biological productivity and biodiversity. Since 2013, the International Bathymetric Chart of the Southern Ocean (IBCSO) has represented the most comprehensive compilation of bathymetry for the Southern Ocean south of 60°S. Recently, the IBCSO Project has combined its efforts with the Nippon Foundation - GEBCO Seabed 2030 Project supporting the goal of mapping the world's oceans by 2030. New datasets initiated a second version of IBCSO (IBCSO v2). This version extends to 50°S (covering approximately 2.4 times the area of seafloor of the previous version) including the gateways of the Antarctic Circumpolar Current and the Antarctic circumpolar frontal systems. Due to increased (multibeam) data coverage, IBCSO v2 significantly improves the overall representation of the Southern Ocean seafloor and resolves many submarine landforms in more detail. This makes IBCSO v2 the most authoritative seafloor map of the area south of 50°S., (© 2022. The Author(s).)

Background: The Coronavirus disease 2019 (COVID-19) pandemic is having a major global impact, and the resultant response in the development of new diagnostics is unprecedented. The detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a role in managing the pandemic. We evaluated the feasibility of using SARS-CoV-2 peptide Kode Technology-modified red cells (C19-kodecytes) to develop an assay compatible with existing routine serologic platforms., Study Design and Methods: A panel of eight unique red cells modified using Kode Technology function-spacer-lipid constructs and bearing short SARS-CoV-2 peptides was developed (C19-kodecyte assay). Kodecytes were tested against undiluted expected antibody-negative and -positive plasma samples in manual tube and three column agglutination technology (CAT) platforms. Parallel analysis with the same peptides in solid phase by enzyme immunoassays was performed. Evaluation samples included >120 expected negative blood donor samples and >140 COVID-19 convalescent plasma samples, with independent serologic analysis from two centers., Results: Specificity (negative reaction rate against expected negative samples) in three different CAT platforms against novel C19-kodecytes was >91%, which correlated with published literature. Sensitivity (positive reaction rate against expected positive convalescent, PCR-confirmed samples) ranged from 82% to 97% compared to 77% with the Abbott Architect SARS-CoV-2 IgG assay. Manual tube serology was less sensitive than CAT. Enzyme immunoassay results with some Kode Technology constructs also had high sensitivity., Conclusions: C19-kodecytes are viable for use as serologic reagent red cells for the detection of SARS-CoV-2 antibody with routine blood antibody screening equipment., (© 2021 The Authors. Transfusion published by Wiley Periodicals LLC. on behalf of AABB.)

The mechanism of formation of the polarimetric signal observed in the spin noise spectroscopy (SNS) is analyzed from the viewpoint of the light scattering theory. A rigorous calculation of the polarimetric signal (Faraday rotation or ellipticity) recorded in the SNS is presented in the approximation of single scattering. We show that it is most correctly to consider this noise as a result of scattering of the probe light beam by fluctuating susceptibility of the medium. Fluctuations of the gyrotropic (antisymmetric) part of the susceptibility tensor lead to appearance of the typical for the SNS Faraday rotation noise at the Larmor frequency. At the same time, fluctuations of linear anisotropy of the medium (symmetric part of the susceptibility tensor) give rise to the ellipticity noise of the probe beam spectrally localized at the double Larmor frequency. The results of the theoretical analysis well agree with the experimental data on the ellipticity noise in cesium vapor.

Invited for this month's cover is the group of Prof. Nicolai Bovin from the Russian Academy of Sciences. The cover picture shows how a biotin residue initially hidden in a monolayer formed on the surface of a material by biot-CMG-DOPE (see top left) is pulled out of the layer by the streptavidin molecule (Str) that has come close to it (see below). This can be considered as a model of certain events (in particular, cis protein-ligand interactions) occurring on the surface of a living cell when it is necessary to hide the ligand from undesirable interactions, but leave the possibility of its recognition by a high-affinity protein. The picture is inspired by the legendary Yellow Submarine cartoon. Read the full text of their Full Paper at https://doi.org/10.1002/open.201900276., (© 2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

The synthetic function-spacer-lipid (FSL) amphiphile biotin-CMG-DOPE is widely used for delicate ligation of living cells with biotin residues under physiological conditions. Since this molecule has an "apolar-polar-hydrophobic" gemini structure, the supramolecular organization is expected to differ significantly from the classical micelle. Its organization is investigated with experimental methods and molecular dynamics simulations (MDS). Although the linear length of a single biotin-CMG-DOPE molecule is 9.5 nm, the size of the dominant supramer globule is only 14.6 nm. Investigations found that while the DOPE tails form a hydrophobic core, the polar CMG spacer folds back upon itself and predominantly places the biotin reside inside the globule or planar layer. MDS demonstrates that <10 % of biotin residues on the highly water dispersible globules and only 1 % of biotin residues in layer coatings are in an linear conformation and exposing biotin into the aqueous medium. This explains why in biotin-CMG-DOPE apolar biotin residues both in water dispersible globules and coatings on solid surfaces are still capable of interacting with streptavidin., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

A rapid and simple method of biofunctionalising nylon, cellulose acetate, and polyvinyl butyral electrospun nanofibers with blood group glycans was achieved by preparing function-spacer-lipid constructs and simply contacting them to fibers with a piezo inkjet printer. A series of water dispersible amphipathic glycan-spacer constructs were synthesized representing a range ABO and related blood group antigens. After immediate contact of the amphipathic glycan-spacer constructs with nanofiber surfaces they self-assembled and were detectable by enzyme immunoassays with high sensitivity and specificity., (© 2016 Wiley Periodicals, Inc.)

Background: Lewis serologic reagents frequently give inaccurate phenotyping results. Furthermore these serologic reagents are often used in nonserologic assays such as inhibition and immunohistochemistry. In both scenarios knowledge of the fine specificity and cross-reactivity of these reagents will improve the quality of results obtained., Study Design and Methods: A range of contemporary and historical workshop and developmental Lewis reagents including mouse monoclonal (MoAb) and human and goat polyclonal (PoAb) reagents were evaluated. All were evaluated both against Lewis kodecytes expressing only single Le(a) , Le(b) , ALe(b) , BLe(b) , Le(x) , Le(y) , ALe(y) , or BLe(y) antigens and against the same antigens inkjet printed on a paper-based microplate and analyzed by enzyme immunoassay. Nine clinical samples were also evaluated. A kodecyte antigen dilution sensitivity assay was used to establish the ratio of Le(b) antigen between group A1 /A2 and O RBCs., Results: A continuum of cross-reactivity from Le(x) through to H was observed with MoAbs. All PoAb and few MoAb anti-Le(a) samples and reagents cross-reacted to some degree with Le(b) antigen. Some PoAb and MoAb anti-Le(b) did not cross-react with Le(a) . All polyclonal goat anti-Le(b) reagents showed substantial activity against ALe(b) and BLe(b) , while no MoAb reagent had this activity. A1 RBCs had less than half the Le(b) antigen of A2 /O RBCs., Conclusions: Substantial cross-reactivity of both MoAbs and PoAbs with related antigens highlights the risks of using serologic reagents in nonserologic assays or against synthetic antigens. The lack of ALe(b) activity in anti-Le(b) MoAbs explains their poor performance against blood group A1 Le(a-b+) phenotypes., (© 2015 AABB.)

Background: Monoclonal (MoAb) reagents are routinely used and are usually very reliable for the serologic determination of ABO blood types. However, the fine specificity and cross-reactivity of these reagents are often unknown, particularly against synthetic antigens used in some diagnostic assays. If nonserologic assays or very sensitive techniques other than those specifically prescribed by the manufacturer are used, then there is a risk of incorrect interpretation of results., Study Design and Methods: Forty-seven MoAbs and two polyclonal ABO reagents were tested against red blood cell (RBC) kodecytes prepared with A trisaccharide, A Type 1, A Type 2, A Type 3, A Type 4, B trisaccharide, B Type 1, B Type 2, acquired B trisaccharide, and Le(a) trisaccharide function-spacer-lipid (FSL) constructs. Natural RBCs were tested in parallel. In addition these FSL constructs were printed onto paper with a desktop inkjet printer and used in a novel immunoassay that identifies reactivity through the appearance of alphanumeric characters., Results: Mapping of MoAbs with kodecytes and printed FSL constructs revealed a series of broad recognition patterns. All ABO MoAbs tested were reactive with the RBC dominant Type 2 ABO antigens. Unexpectedly some anti-A reagents were reactive against the B Type 1 antigen, while others were poorly reactive with trisaccharide antigens., Conclusions: All ABO MoAbs detect the RBC dominant Type 2 ABO antigens; however, some reagents may show minor reactivity with inappropriate blood group antigens, which needs to be considered when using these reagents in alternative or highly sensitive analytic systems., (© 2014 AABB.)

Adhesion/growth-regulatory galectins (gals) exert their functionality by the cis/trans-cross-linking of distinct glycans after initial one-point binding. In order to define the specificity of ensuing association events leading to cross-linking, we recently established a cell-based assay using fluorescent glycoconjugates as flow cytometry probes and tested it on two human gals (gal-1 and -3). Here we present a systematic study of tandem-repeat-type gal-4, -8 and -9 loaded on Raji cells resulting in the following key insights: (i) all three gals bound to oligolactosamines; (ii) binding to ligands with Galβ1-3GlcNAc or Galβ1-3GalNAc as basic motifs was commonly better than that to canonical Galβ1-4GlcNAc; (iii) all three gals bound to 3'-O-sulfated and 3'-sialylated disaccharides mentioned above better than that to parental neutral forms and (iv) histo-blood group ABH antigens were the highest affinity ligands in both the cell and the solid-phase assay. Fine specificity differences were revealed as follows: (i) gal-8 and -9, but not gal-4, bound to disaccharide Galβ1-3GlcNAc; (ii) increase in binding due to negatively charged substituents was marked only in the case of gal-4 and (iii) gal-4 and -8 bound preferably to histo-blood group A glycans, whereas gal-9 targeted B-type glycans. Experiments with single carbohydrate recognition domains (CRDs) of gal-4 showed that the C-CRD preferably bound to ABH glycans, whereas the N-CRD associated with oligolactosamines. In summary, the comparative analysis disclosed the characteristic profiles of glycan reactivity for the accessible CRD of cell-bound gals. These results indicate the distinct sets of functionality for these three members of the same subgroup of human gals.

The network of adhesion/growth-regulatory galectins in chicken (chicken galectin, CG) has only one tandem-repeat-type protein, CG8. Using a cell-based assay and probing galectin reactivity with a panel of fluorescent neoglycoconjugates (glycoprobes), its glycan-binding profile was determined. For internal validation, human galectin-8 (HG8) was tested. In comparison to HG8, CG8 showed a rather similar specificity: both galectins displayed high affinity to blood group ABH antigens as well as to 3'-sialylated and 3'-sulfated lactosamine chains. The most remarkable difference was found to be an ability of HG8 (but not CG8) to bind the disaccharide Galβ1-3GlcNAc (Le(c)) as well as branched and linear oligolactosamines. The glycan-binding profile was shown to be influenced by glycocalix of the cell, where the galectin is anchored. Particularly, glycosidase treatment of galectin-loaded cells led to the change of the profile. Thus, we suppose the involvement of cis-glycans in the interaction of cell-anchored galectins with external glycoconjugates.

Management of exudative otitis media is a challenging problem in view of its high prevalence and frequent complications in the form of stable hearing loss. The highest morbidity rate is documented among 25 and 50-year old subjects which accounts for the substantially reduced level of social activity associated with this disease. Clinical examination and audiologic techniques are frequently insufficient to diagnose exudative otitis media. Computed tomography provides a reliable tool for the exact diagnosis, optimal choice of treatment strategy, and evaluation of its efficacy during dynamic observations.

The experiments on 286 mice of two lines (SHR and C57BL/6) showed that 3-indoipyruvate, a natural keto analogue of tryptophan and a precursor of serotonin and kynurenic acid) possesses the selective dose-dependent (100-500 mg/kg, intraperitoneally) protective effect against quinolinate-induced convulsions. At prolonged administration (50-100 mg/kg for 10 days twice a day) its efficiency drastically increased. It is supposed that the mechanism of the anticonvulsant action of 3-indolpyruvate involves an enhancement of synthesis of kynurenic acid, a blocker of N-methyl-D-aspartate receptors, and at chronic administration--also an increase of sensitivity and density of these receptors.

The role of the endogenous convulsant kynurenine (K) in the mechanisms of the development of epileptic seizures in alcoholic persons was studied on a clinical material of 63 patients suffering from alcoholism with the presence on the EEG of paroxysmal alterations without epileptic fits (n = 28) and alcoholic epilepsy (n = 35), epileptic patients not abusing alcohol (n = 20), and practically healthy subjects (n = 10). There was a significant increase of the K concentration in alcoholic patients with paroxysmal disturbances on the EEG or convulsive seizures. That increase directly correlated with the rate of convulsive epileptic fits. The rise of K in patients with alcoholic epilepsy was lower than in epileptic patients, being, however, significantly higher than in practically healthy subjects abusing alcohol and having but paroxysmal alterations on the EEG (without seizures).

Behaviour of SHR, C57B1/6 male mice and common albino male rats treated intracerebroventricularly or intraperitoneally with kynurenine, quinolinic, kynurenic, picolinic, xanthurenic, anthranilic acids and nicotinamide, was studied in the dark/light chamber. Quinolinic acid and its precursor kynurenine diminished dark preference, increased the number of transitions between dark and light compartments, diminished locomotion in light compartment. Biogenic amine phenylethylamine with its typical anxiogenic activity, exerted a similar action. Diazepam acted in the opposite way. Noncompetitive antagonist of the NMDA receptors, kynurenic acid, prevented the effect of quinolinic acid. The hole reflex appears to be a useful simple object to study neuroactive endogenous compounds on.

As many as 30 patients with affective psychoses were examined for the concentration of plasma kynurenine, a neuroactive tryptophan metabolite, and for the parameters of the dexamethasone test. A group of patients suffering from "endogenous anxiety" and endogenous depression were distinguished. In the patients' group with "endogenous anxiety", the concentration of kynurenine at the height psychosis was significantly higher as compared to controls, correlating with the gravity of anxious symptomatology. In the patients' group with endogenous depression, plasma kynurenine was significantly lower than in controls but did not agree with the depression gravity. The dexamethasone test appeared pathological only in the group of patients suffering from endogenous depression and its parameters correlated well with the gravity of depressive symptomatology. In both groups, the study parameters returned to normal after the egress from the morbid condition.

All excitatory amino acid antagonists studied: diethyl esters of aspartic (DEEA) and glutamic (DEEG) acids, 2-amino-3-phosphono-propionic acid (APPA) and 2-amino-4-phosphono-butanoic acid (APBA), diminished the amplitude of excitatory postsynaptic potentials (EPP) of the locust (Locusta migratoria migratorioides) muscle fibers and arbitrary blocked glutamate (GLU) and aspartate (ASP) responses. Kynurenine (KYN) and quinolinic (QUI) acid had no effect on EPP even at a concentration of 2 X 10(-2) M. The antagonists were not strictly selective against intracerebroventricularly administered endogenous convulsants: GLU, ASP, KYN and QUI and in simulation of experimental seizures in mice. The antagonists structurally similar to ASP prevented ASP- and KYN-induced seizures in lower doses than GLU derivatives. Anti-KYN, but not anti-QUI DEEA, DEEG, APPA and APBA efficacy suggests that KYN and QUI act on different structures or binding sites.

Benzobarbital, primidone, phenobarbital, phynytoin and trimethadionum (in order of decreasing activity) were moderately effective against DL-kynurenine (50 micrograms, i. c. v.)-induced seizures in SHR albino male mice. Diazepam was ineffective even in doses of 15 and 25 mg/kg. Against seizures induced by quinolinic acid (5 micrograms, i. c. v.) anticonvulsants, particularly primidone and phenytoin, were more effective than against kynurenine-induced seizures. Diazepam was slightly effective in high doses of 7-15 mg/kg. Primidone and benzobarbital in doses used (10-50 mg/kg) were ineffective against strychnine and pentylenetetrazol. Selective efficacy of primidone and benzobarbital in this model of seizures suggests that kynurenine and quinolinic acid could be involved in the grand mal fits in epileptic patients.

Phenibut, sodium hydroxybutyrate and baclofen are selectively effective against seizures induced in mice by the endogenous metabolites of tryptophan, L-kynurenine and quinolinic acid. The seizures were not affected by the drugs in doses under study. Depakine and aminooxyacetic acid as well as diazepam and phenobarbital appeared the most effective against pentylenetetrazole seizures. GABA and muscimol administered intracerebroventricularly merely prolonged the latency of seizures. Dissimilarities in the GABA-ergic mechanisms of the anticonvulsant effects of the drugs under consideration are discussed.

It has been shown in the behavioural experiments that combined pretreatment with haloperidol (0.25 mg/kg) and caerulein (40 micrograms/kg), and to a lesser extent pretreatment with caerulein alone caused long-term reversal of amphetamine (2 mg/kg) induced hyperexcitability in rats. Administration of proglumide (50 mg/kg), an antagonist of CCK-8 receptors, did not reverse long-term antiamphetamine effect of caerulein. In mice pretreatment with caerulein (50 and 100 micrograms/kg) alone or in combination with haloperidol (0.25 mg/kg) caused hypersensitivity to the behavioural effect of amphetamine (3 mg/kg). Intraventricular (I ng), but not systemic (100-500 micrograms/kg) administration of caerulein selectively antagonized seizures in mice induced by intraventricular administration of quinolinic acid (5 micrograms) and N-methyl-D-aspartate (0.2 microgram). Pretreatment with proglumide (50 mg/kg) reversed the anticonvulsive effect of caerulein in mice. In rats, caerulein failed to affect the seizures caused by intraventricular administration of quinolinic acid. The results of the present study demonstrate the existence of obvious interspecies differences in the behavioural effects of caerulein, the agonist of CCK-8 receptors, in mice and rats.

Derivatives of GABA which are ineffective against seizures produced by typical convulsants (strychnine, pentylenetetrazole, etc.), phenibut and sodium hydroxybutyrate in doses of 200 mg/kg and higher possess marked anticonvulsant action against seizures induced by intraventricular injection of L-kynurenine and quinolinic acid in mice. Phepiron, a cyclic form of phenibut, had dissimilar action on the effects of L-kynurenine and a quinolinic acid, enhancing that produced by the former agent and diminishing tonic extension and lethality after the latter one. GABA and piracetam appeared to be ineffective. Efficacy of GABA derivatives against seizures produced by L-kynurenine and quinolinic acid suggests that the system of GABA plays a significant role in the genesis of seizures produced by kynurenines.

A total of 84 children were investigated: 15 with bronchial asthma, 41 with combined seizure and bronchial obstruction syndrome, 14 with epilepsy. The kynurenine blood level was found to correlate with seizures. It was highest in epilepsy (5.27 +/- 0.99 nM/ml) together with the lowest dioxygenase activity (0.53 +/- 0.29 nM/ml) as measured with the tryptophane loading. The data suggest that kynurenine being a major tryptophane metabolite plays a role in pathogenesis of convulsive states.

A comparative study of the influence of kynurenic acid (KYNA), L-kynurenine (KYN) and ethylimidazole-4-5-dicarboxylic acid (IEM-1442) on neuro-destructive effect of quinolinic acid (QUIN) in hippocampal cell cultures of mouse embryos and on convulsive action of QUIN after its injection into the brain ventricles of adult mice was performed. In presence of KYNA the neuronal destruction in vitro didn't occur under QUIN exposure, while in situ KYNA had no effect on convulsive action of QUIN. On the other hand, KYN and IEM-1442 didn't block the neurodegenerative action of QUIN in vitro, whereas in situ these compounds showed the anticonvulsant, effect. The results obtained suppose, that some anticonvulsants, preventing convulsive effects of QUIN, are not antagonists of the receptors, which mediate its neurodegenerative action.

There is presented a brief review of the authors' and literature data on the excitatory and convulsant effects of kynurenines, mainly 1-kynurenine and quinolinic acid. Particular attention is given to the interactions of kynurenines with the excitatory and inhibitory amino acids, their receptors, benzodiazepine receptor complex, catecholamines, serotonin, acetylcholine. The following trends of studies on the neuroactivity of kynurenines seem to be promising: isolation of specific binding sites for the most active kynurenines--kynurenine, quinolinic and kynurenic acids, the interaction with other endogenous convulsants like beta-carbolines, endorphines, folates, etc., the search of the brain structures triggering or deferring the excitatory and convulsant effects of kynurenines.

Selective antagonists of quinolinic acid (2,3-pyridine dicarboxylic acid, QUIN)--an endogenous convulsant tryptophan metabolite, administered intracerebroventricular to mice, were identified during comparison with the following intracerebroventricular convulsants: l-kynurenine, aspartic, glutamic, N-methyl-DL-aspartic and kainic acids. It is suggested that the antagonism arises due to a common fragment of the structure which consists of two carboxylic groups at two nearest carbon atoms of the ring and of one nitrogen atom in the alpha-position. The selective action of the compounds found against QUIN supports the suggestion that QUIN produces seizures via N-methyl-D-aspartate binding sites.

In frogs (Rana temporaria) injection of L-kynurenine, quinolinic, nicotinic and picolinic acids (10 microgram) into brain ventricles potentiated the stimulant ad convulsant effects of a subthreshold dose of strychnine. Xanthurenic and anthranilic acids were ineffective. At a dose of 100 micrograms picolinic acid produced seizures in 25% of animals, quinolinic acid and L-kynurenine motor excitement in all animals, and the action of nicotinic acid was shown by severe muscle hypotonus. The doses lower than 100 g proved inactive.

Antidepressants-thymoanaleptics chlorimipramine, amitriptyline, imipramine, melitracen potenciated the inhibitory effect of reserpine in a frog (supression of the turning over from the back reflex) stronger than did antidepressants with less marked thymoanaleptic action (Lu-5-003, azaphen, quipazine, desipramine) and also neuroleptics (promazine, stelazine, haloperidol) cholinolytics (atropine and benectyzine) and stimulator--phenamine. The potentiating action of tertiary amines--imipramine, amitriptyline protixen was stronger than that of the corresponding secondary amines (desipramine, norprotixen, nortriptyline). Phenothiazines with the chlorine atom in the second position (chlorprotixen and chlorpromazine) potentiated the effect of reserpine less intensively than did their chlorine-free analogues (protixen, promazine).

In experiments on mice the existence of common mechanisms of action was revealed in picrotoxin and kynurenine and quinolinic acid. Picrotoxin selectively potentiated convulsions induced by kynurenine and quinolinic acid and the antagonists of these endogenous convulsants--picolinic, kynurenic and xanthurenic acids--selectively antagonized picrotoxin convulsions. GABA-ergic preparations, effective in kynurenine convulsions and the anticonvulsants diazepam and phenobarbital, were highly effective against picrotoxin-induced convulsions also. Puphemid and trimethin indicated for treating petit mal epilepsy, proved ineffective. The obtained data suggest the possibility of action of kynurenine and quinolinic acid via picrotoxin-sensitive subunits of the benzodiazepine-GABA-receptor-ionophore complex.

Concentration of neuroactive tryptophane--kynurenine metabolite was studied in healthy men volunteers in conditions of anxiety artificially elicited by caffeine. At peak of the alarm the level of the kynurenine significantly increased and came to norm after anxiety cessation. Possible causes of this increase are discussed. High correlation has been obtained between the kynurenine concentration and initial values of personal and reactive anxiety. The conclusion is made about the participation of the kynurenine in formation of personal and reactive anxiety in man.