Synthesis and pharmacological evaluation of new 5-(cyclo)alkyl-5-phenyl- and 5-spiroimidazolidine-2,4-dione derivatives. Novel 5-HT1A receptor agonist with potential antidepressant and anxiolytic activity.

The synthesis of 5-(cyclo)alkyl-5-phenyl- and 5-spiroimidazolidine-2,4-dione derivatives with an arylpiperazinylpropyl moiety (12-23) and their in vitro and in vivo pharmacological properties and molecular characteristics were described. The investigated compounds exhibited high affinity for 5-HT(1A) (13-22) and 5-HT(2A) (18, 20, 21, 23) receptors and diversified pharmacological profile. Compounds 17, 20 and 22 showed antagonistic, partial agonistic and agonistic activity, respectively, toward 5-HT(1A) receptor and they were investigated as potential antidepressants and/or anxiolytics.

Information causality as a physical principle.

Quantum physics has remarkable distinguishing characteristics. For example, it gives only probabilistic predictions (non-determinism) and does not allow copying of unknown states (no-cloning). Quantum correlations may be stronger than any classical ones, but information cannot be transmitted faster than light (no-signalling).

AAN82231 protein from uropathogenic E. coli CFT073 is a close paralog of DsbB enzymes and does not belong to the DsbI family.

Dsb proteins control the formation and rearrangement of disulfide bonds during the folding of membrane and exported proteins. DsbA is an oxidant that catalyzes formation of disulfide bonds in newly synthesized, and yet unfolded proteins. In order to act catalytically again, it has to be reoxidized by a transmembrane protein DsbB characterized by two pairs of disulfides.

Identification and classification of bcl genes and proteins of Bacillus cereus group organisms and their application in Bacillus anthracis detection and fingerprinting.

The Bacillus cereus group includes three closely related species, B. anthracis, B. cereus, and B.

Synthesis and preliminary pharmacological evaluation of imidazo[2,1-f]purine-2,4-dione derivatives.

A series of N-8-arylpiperazinylpropyl derivatives of 1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4-dione (2-10) and amide derivatives of 1,3-dimethyl-6,7-dihydroimidazo[2,1-f]purine-2,4-(1H,3H)-dione-7-carboxylic acid (11-13) were synthesized. Compounds (2-10) evaluated in vitro were potent 5-HT(1A) receptor ligands. Preclinical studies indicated that 8-[3-(N4-phenyl)-piperazin-N1-yl-propyl]-1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4-dione (2) exerts anxiolytic-like activity in the four-plate test in mice; however its effect was weaker, than that produced by Diazepam.

Postnatal expression pattern of HCN channel isoforms in thalamic neurons: relationship to maturation of thalamocortical oscillations.

Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels are the molecular substrate of the hyperpolarization-activated inward current (I(h)). Because the developmental profile of HCN channels in the thalamus is not well understood, we combined electrophysiological, molecular, immunohistochemical, EEG recordings in vivo, and computer modeling techniques to examine HCN gene expression and I(h) properties in rat thalamocortical relay (TC) neurons in the dorsal part of the lateral geniculate nucleus and the functional consequence of this maturation. Recordings of TC neurons revealed an approximate sixfold increase in I(h) density between postnatal day 3 (P3) and P106, which was accompanied by significantly altered current kinetics, cAMP sensitivity, and steady-state activation properties.

Sulfonamides with the N-alkyl-N'-dialkylguanidine moiety as 5-HT7 receptor ligands.

A series of arylsulfonamides containing guanidine incorporated in the structure of secondary amines (piperidine, piperazine) was synthesized on SynPhase Lanterns and evaluated for 5-HT(1A), 5-HT(2A), and 5-HT(7) receptors. The results demonstrated that N-alkyl-N'-dialkylguanidines displayed good 5-HT(7)/5-HT(1A) selectivity and may be regarded as promising structural core for development of 5-HT(7) ligands.

Combinatorial chemistry on solid support in the search for central nervous system agents.

The advent of combinatorial chemistry was one of the most important developments, that has significantly contributed to the drug discovery process. Within just a few years, its initial concept aimed at production of libraries containing huge number of compounds (thousands to millions), so called screening libraries, has shifted towards preparation of small and medium-sized rationally designed libraries. When applicable, the use of solid supports for the generation of libraries has been a real breakthrough in enhancing productivity.

Decreasing concentration of interstitial glucose in REM sleep in subjects with normal glucose tolerance.

Aims: Sleep is divided into two major stages, non-rapid eye movement (NREM) and rapid eye movement (REM), which are distinct in various neuroendocrine respects. NREM/REM cycles influence insulin and glucagon secretion; however, glucose concentrations in REM compared with NREM have not been directly explored. The aim was to investigate the differences in glucose concentrations in interstitial fluid (IGC) between NREM/REM cycles using a continuous glucose monitoring system (CGMS).

Monogamy of Bell's inequality violations in nonsignaling theories.

We derive monogamy relations (tradeoffs) between strengths of violations of Bell's inequalities from the nonsignaling condition. Our result applies to general Bell inequalities with an arbitrary large number of partners, outcomes, and measurement settings. The method is simple, efficient, and does not require linear programing.

Interactive effects of spectral shading and mechanical stress on the expression and costs of shade avoidance.

The interacting effects of different environmental cues in determining a plant's phenotype and performance are poorly understood aspects of phenotypic plasticity. We examined the interacting effects of shading and mechanical stress (MS) on growth, reproduction, and mechanical stability. We subjected 10 grassland genotypes and 10 forest genotypes of Impatiens capensis to two levels of spectral shading and two levels of MS.

MetaMQAP: a meta-server for the quality assessment of protein models.

Background: Computational models of protein structure are usually inaccurate and exhibit significant deviations from the true structure. The utility of models depends on the degree of these deviations. A number of predictive methods have been developed to discriminate between the globally incorrect and approximately correct models.

The influence of an ethylene spacer on the 5-HT(1A) and 5-HT(2A) receptor affinity of arylpiperazine derivatives of amides with N-acylated amino acids and 3-differently substituted pyrrolidine-2,5-diones.

A library of ethylene analogs of the previously described arylpiperazines with N-acylated amino acids was synthesized on SynPhase Lanterns and the library representatives were evaluated for their 5-HT(1A) and 5-HT(2A) receptor affinities. The obtained results were compared with those reported for compounds containing propylene and a butylene spacer and they revealed that 5-HT(1A) receptor affinity decreased proportionally with the length of the alkyl chain. Furthermore, the synthesized 3-cycloalkyl derivatives containing two methylene group spacers showed that the 3-position of pyrrolidine-2,5-dione preferred substituents of hydrophobic character.

Reciprocal modulation of I (h) and I (TASK) in thalamocortical relay neurons by halothane.

By combining electrophysiological, immunohistochemical, and computer modeling techniques, we examined the effects of halothane on the standing outward current (I (SO)) and the hyperpolarization-activated current (I (h)) in rat thalamocortical relay (TC) neurons of the dorsal lateral geniculate nucleus (dLGN). Hyperpolarizing voltage steps elicited an instantaneous current component (I (i)) followed by a slower time-dependent current that represented I (h). Halothane reduced I (h) by shifting the voltage dependency of activation toward more negative potentials and by reducing the maximal conductance.

Circadian blood pressure variation in normotensive type 2 diabetes patients and angiotensin converting enzyme polymorphism.

Background/aims: Loss of circadian blood pressure (BP) variation (i.e., lack of nocturnal BP dip by at least 10mmHg, 'non-dipping') is associated with increased mortality rate in subjects with diabetes.

G/A polymorphism at -258 of the hepatic glucokinase promoter is not associated with decreased birth weight in preterm neonates.

Background: A high percentage of preterm neonates are born small for gestational age (SGA). These children show a high morbidity and mortality after birth and often develop insulin resistance with ensuing impaired glucose metabolism in adulthood. Since insulin is important for intrauterine growth, fetal insulin resistance might also influence birth weight of preterm neonates.

Tip-alpha (hp0596 gene product) is a highly immunogenic Helicobacter pylori protein involved in colonization of mouse gastric mucosa.

A product of the Helicobacter pylori hp0596 gene (Tip-alpha) is a highly immunogenic homodimeric protein, unique for this bacterium. Cell fractionation experiments indicate that Tip-alpha is anchored to the inner membrane. In contrast, the three-dimensional model of the protein suggests that Tip-alpha is soluble or, at least, largely exposed to the solvent.

Ferromagnetic spins interaction in poly(m-p-aniline).

Alternating poly(m-p-aniline) can be oxidized to radical cations with spins S = 1/2. For high spin density, ferromagnetic spin interaction is observed, and some of the generated radical cations are found to be in a ground triplet state.

Circadian blood pressure variation and antihypertensive medication adjustment in normoalbuminuric type 2 diabetes patients.

Background/aims: The aim of the study was to assess the effect of an antihypertensive treatment adjustment on 24-hour blood pressure variation in type 2 diabetes patients.

Methods: The study group included 59 hypertensive type 2 diabetes patients subjected to a single one-step antihypertensive agent dose adjustment (increase or decrease). Ambulatory blood pressure monitoring was performed at baseline and 4-6 weeks after the treatment modification.

7-Arylpiperazinylalkyl and 7-tetrahydroisoquinolinylalkyl derivatives of 8-alkoxy-purine-2,6-dione and some of their purine-2,6,8-trione analogs as 5-HT(1A), 5-HT(2A), and 5-HT(7) serotonin receptor ligands.

On the basis of our earlier studies with the serotonin receptor ligands in the group of 1,3-dimethyl-3,7-dihydropurine-2,6-dione derivatives, a series of new arylpiperazinylalkyl and tetrahydroisoquinolinylalkyl analogs of 8-alkoxy-1,3-dimethyl-3,7-dihydropurine-2,6-dione (10-25) and 1,3-dimethyl-7,9-dihydro-3H-purine-2,6,8-trione (26-30) were synthesized and their 5-HT(1A), 5-HT(2A), and 5-HT(7) receptor affinities were determined. The new compounds 17, 18, 20, and 21 were found to be highly active 5-HT(1A) receptor ligands (K(i)=11-19nM) with diversified affinity for 5-HT(2A) receptors (K(i)=15-253nM). Compounds 12, 13, 15, and 19 were moderately potent 5-HT(2A) ligands (K(i)=23-57nM), whereas 17, 18, 24, and 25 showed distinct affinity for 5-HT(7) receptors (K(i)=51-83nM).

Predicting maximum Roux-en-Y gastric bypass-induced weight reduction--preoperative plasma leptin or body weight?

Background: Weight loss after bariatric surgery varies between patients, and predicting the extent thereof is often inaccurate. The aim of this study was to assess the potential of preoperative plasma leptin and body weight in predicting the maximum weight loss within 2 years after Roux-en-Y gastric bypass (RYGBP).

Methods: The study comprised 68 subjects (39 women, 29 men; mean age 36.

Distribution of the components of the NCEP ATP III-defined metabolic syndrome in newly diagnosed diabetes and non-diabetes caucasian subjects; implications for metabolic syndrome prevention and treatment.

Unlabelled: The study aimed at assessing the relationship between five components of the NCEP ATP III-defined metabolic syndrome (MS) in diabetes and non-diabetes MS subjects.

Methods: Prevalence of MS and its components was assessed in 1586 adult Caucasian individuals, without known diabetes. Oral glucose tolerance test (OGTT) with 75 g glucose according to WHO protocol was conducted in all subjects.

Genetic characterisation of the cjaAB operon of Campylobacter coli.

We investigated the regulation of the cjaA and cjaB genes of Campylobacter coli. These genes are seemingly arranged into one operon but appear to encode functionally different proteins i.e.

Novel class of arylpiperazines containing N-acylated amino acids: their synthesis, 5-HT1A, 5-HT2A receptor affinity, and in vivo pharmacological evaluation.

Novel arylpiperazines with N-acylated amino acids, selected on the basis of a preliminary screening of two libraries previously synthesized on SynPhase Lanterns, were prepared in solution and their affinity for 5-HT(1A), 5-HT(2A), and D(2) receptors was evaluated. The compounds bearing (3-acylamino)pyrrolidine-2,5-dione (19-26) and N-acylprolinamide (29-34) moieties showed high affinity for 5-HT(1A) (K(i)=3-47 nM), high-to-low for 5-HT(2A) (K(i)=4.2-990 nM), and low for D(2) receptors (K(i)=0.

High-spin radical cations of alternating poly(m-p-anilines).

Three alternating poly(m-p-anilines) have been synthesized via palladium-catalyzed amination reactions. Polymers were oxidized to radical cations by the use of chemical and electrochemical methods. The presence of radical cations was manifested by the appearance of two new bands in UV-vis spectra and a strong EPR signal.