Locomotor reactions and excitability of neurons during the blockade of dopamine by haloperidol in vertebrate and invertebrate animals

Two groups of rats with different level of motor activities: high- and low-active animals, were distinguished. The blockade of dopamine receptors by haloperidol led to depression of locomotor activity in both groups of rats; in grape snails, haloperidol caused a decrease of the velocity of locomotor responses. In was found that within 5 minutes of intravenous injection of haloperidol the excitability of spinal centers of rats decreased; but in 30 minutes in started restoring. Chronic application of the preparation depressed the effect of posttetanic potentiation of H-response in gastrocnemius muscle of spinal rats. In command neurons of grape snail, chronic injections of haloperidol causes a significant hyperpolarization shift of membrane potential and an increase of threshold of the generation of action potential. It was shown that the selective pharmacological inhibition of dopaminergic system of the brain led to a decrease of excitability in some determined neurons of the snail and spinal motor centers of rats, as well as inhibited the locomotor responses both in vertebrate and in invertebrate animals.     

Orthologous gene-expression profiling in multi-species models: search for candidate genes

Microarray-driven gene-expression profiles are generally produced and analyzed for a single specific experimental model. We have assessed an analytical approach that simultaneously evaluates multi-species experimental models within a particular biological condition using orthologous genes as linkers for the various Affymetrix microarray platforms on multi-species models of ventilator-associated lung injury. The results suggest that this approach may be a useful tool in the evaluation of biological processes of interest and selection of process-related candidate genes.     

Synthesis and biologically relevant properties of polyphosphazene polyacids

Polyphosphazene polyacids show potential as immunostimulating compounds and materials for microencapsulation. Their synthesis requires multistep chemical transition from a hydrolytically unstable macromolecular precursor, poly(dichlorophosphazene), to a water-soluble polyelectrolyte. Insufficient synthetic control in these reactions can lead to molecular weight variations and formation of macromolecules with "structural defects" resulting in significant variations in polymer performance. Simple and reproducible "one pot-one solvent" method is reported for the preparation of polyphosphazene polyacids-poly[di(carboxylatophenoxy)phosphazene] and its copolymers. Molecular weight characteristics and polymer compositions were studied as a function of reaction parameters. Macromolecular byproducts, incompletely substituted polymers containing hydroxyl groups and partially deprotected polymers containing propyl ester functionalities, were synthesized and characterized. It was demonstrated, that the presence of such groups can affect polymer characteristics, such as hydrolytic degradation profiles, immunostimulating activity, and microsphere forming properties. In vivo studies showed that the immunostimulating activity of polyphosphazene polyacids correlates with the content of acid functionalities in the polymer.     

Model of three dimensional structure of the immunodominant epitope of gp120 HIV(Thailand)

The geometry of five preferred structures of the immunodominant epitope of the HIV(Thailand) protein gp120, derived earlier from the NMR spectroscopy data, was refined using the quantum chemical methods. As a result, (i) the energy characteristics of the initial structures were improved significantly, (ii) their relative locations on the scale of formation heats were determined, and (iii) the energy barriers dividing the conformers under study were computed. On this basis, only two out of five starting structures were proposed as biologically relevant conformations for the virus immunogenic crown. The results obtained are discussed in connection with the literature data on the structure of the HIV-1 principal neutralizing determinant.     

Structure and conformational properties of the HIV Thailand gp120 immunodominant epitope

NMR data and the previously developed theoretical method were used to determine the three-dimensional structure of the immunodominant epitope (IDE) of the HIVThailand. protein gp120. The best energy IDE conformers consistent with the theoretical and experimental data were calculated, and their ensemble was shown to give rise to the main chain folds found earlier in examining the HIVMN IDE structure. The gp120 IDE is supposed to behave as a metastable oligopeptide that, depending on the microenvironment, largely assumes one of the conformations from the ensemble. The results are discussed in the light of literature data on HIV-1 IDE structure.     

Lack of evidence of an interaction between leu-enkephalin and muscarinic-like responses in the frog semicircular canal

Using multiunit recording of action potentials from the whole vestibular nerve, we studied whether opioid peptide leu-enkephalin (Enk) may modulate muscarinic-like responses in semicircular organs of the frog. When acetylcholine (ACh) (0.1-1 mM) was applied with 1 nM Enk, the maximal frequency increase induced by ACh was reduced.However,the frequency decrease of ACh responses under Enk did not differ from the frequency decline in basal spike discharge induced by Enk alone. Administration of atropine (1 microM) left the response to Enk intact and blocked the excitatory effect of ACh. No modification of the ACh response under Enk was observed in the presence of the non-selective opioid receptor antagonist naloxone (10 microM). This study suggests that no interaction exists between the ACh-mediated excitatory action on resting activity in the isolated semicircular canal preparation and the suppressive action of Enk.     

Structure and polymorphism of the principal neutralization site of Thailand HIV-1 isolate

Refining the geometric parameters for the ensemble of conformers, derived earlier in terms of NMR-spectroscopy data for the immunogenic tip of Thailand HIV-1 isolate, was carried out by quantum chemical methods. As a result, (i) the energy characteristics of initial structures were significantly improved, (ii) their relative locations on the scale of formation heats were determined, and (iii) the energy barriers between conformers under study were computed. On the basis of all data obtained, the high resolution 3D structure model, describing the set of stable conformers and containing the biologically active conformation, was proposed for neutralizing epitope of Thailand HIV-1 isolate. The following major conclusions were made based on the analysis of simulated conformations: i) the Gly-Pro-Gly-Gln-Val-Phe stretch forming the immunogenic crown of Thailand HIV-1 isolate exhibits the properties characteristic for metastable oligopeptide that constitutes in solution the dominant structure with other conformations admissible; (ii) three structures out of five NMR-based starting models form the cluster of conformers which adequately describes general conformational features of this functionally important site of gp120; (iii) two structures residing in this cluster are found to be well-ground for implementing the function of immunoreactive conformation of the stretch of interest; (iv) in spite of this observation, the "global" structure which gives rise to inverse gamma-turn in the central Gly-Pro-Gly crest of Thailand HIV-1 gp120 is proposed to be the most probable conformation responsible for the formation of viral antigen-antibody complex in particular case under study.     

Physiological Heterothallism and Sexuality in Euascomycetes: A Partial History

Copyright 1998 Academic Press.