IL-1 receptor antagonist as an aerosol in inflammation.

The feasibility of efficient aerosol delivery of the human IL-1 receptor antagonist (IL-1Ra) for reduction of acute lung inflammation was demonstrated in a mouse model study. The therapeutic efficacy of dry powder formulations PM(2), PM(10) of IL-1Ra was studied at nonforced inhalation in an aerosol chamber using the DPI "Spinhaler". Micronized powder formulations for insufflation were produced by air-jet milling. The anti-inflammatory effect of IL-Ra preparation was assessed by differential cell counts and biochemical composition of bronchoalveolar lavage (BAL). Reactive oxygen species (ROS), metabolic parameters of BAL (pH, redox potential, total protein, and lactate), and morphological lung changes were investigated by methods of luminol-dependent chemoluminescence, electrochemistry, microscopy, optical, and NMR spectroscopy. Inhalation of IL-1Ra aerosol ensured the systemic absorption of IL-1Ra in the circulatory system and reduced the acute inflammatory response to intranasal lipopolysaccharide challenge. The inhaled anti-inflammatory dosage in aerosol administration appeared to be comparable with i.p. injection. The mechanism of positive action of pulmonary aerosol delivery of Il-Ra includes normalization of the oxidative activity of bronchoalveolar cells, prevention of neutrophil recruitment to the bronchoalveolar tract, and improving of cell respiration. The results were used to develop mathematical models of the anti-inflammatory effects of IL-Ra as functions of the doses and dispersion grades of IL-Ra preparations. Aerosol application of IL-Ra may be an apparent way for prophylactic treating of respiratory inflammation caused by bacterial antigens.     

Synthetic glycovaccine protects against the bite of leishmania-infected sand flies

Leishmaniasis is a vectorborne disease transmitted to human and other mammalian hosts by sand fly bite. In the present study, we show that immunization with Leishmania mexicana promastigote secretory gel (PSG) or with a chemically defined synthetic glycovaccine containing the glycans found in L. mexicana PSG can provide significant protection against challenge by the bite of infected sand flies. Only the glycan from L. mexicana was protective; those from other species did not protect against L. mexicana infection. Furthermore, neither PSG nor the glycovaccine protected against artificial needle challenge, which is traditionally used in antileishmanial vaccine development. Conversely, an antigen preparation that was effective against needle challenge offered no protection against sand fly bite. These findings provide a new target for Leishmania vaccine development and demonstrate the critical role that the vector plays in the evaluation of candidate vaccines for leishmaniasis and other vectorborne diseases.     

Dissociation of early evoked cortical activity in perceptual grouping

Perceptual grouping is a multi-stage process, irreducible to a single mechanism localized anatomically or chronometrically. To understand how various grouping mechanisms interact, we combined a phenomenological report paradigm with high-density event-related potential (ERP) measurements, using a 256-channel electrode array. We varied the relative salience of competing perceptual organizations in multi-stable dot lattices and asked observers to report perceived groupings. The ability to discriminate groupings (the grouping sensitivity) was positively correlated with the amplitude of the earliest ERP peak C1 (about 60 ms after stimulus onset) over the middle occipital area. This early activity is believed to reflect spontaneous feed-forward processes preceding perceptual awareness. Grouping sensitivity was negatively correlated with the amplitude of the next peak P1 (about 110 ms), which is believed to reflect lateral and feedback interactions associated with perceptual awareness and attention. This dissociation between C1 and P1 activity implies that the recruitment of fast, spontaneous mechanisms for grouping leads to high grouping sensitivity. Observers who fail to recruit these mechanisms are trying to compensate by using later mechanisms, which depend less on stimulus properties such as proximity. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.

Complexity of electrocortical dynamics in children: developmental aspects

Dimensional complexity (DCx) is an EEG measure derived from nonlinear systems theory that can be indicative of the global dynamical complexity of electrocortical activity. This study examined developmental changes in DCx, as well as the effects of cognitive tasks, gender, and brain topography, and compared DCx with traditional spectral power measures. EEG was recorded in three groups of children at mean age of 7.5 (n = 37), 13.8 (n = 42), and 16.4 (n = 56) years at rest and during the performance of verbal and spatial cognitive tasks. DCx measured both at rest and during tasks increased with age. Specific effects of brain topography, condition, and gender became stronger with age, suggesting an increase in structural and functional differentiation of the cortex. Hemispheric asymmetry of DCx recorded during tasks also increased with age, with the task-induced DCx reduction being stronger in the left hemisphere. Gender differences in DCx suggested faster cerebral maturation in girls over late adolescence. Relationships between DCx and spectral power varied as a function of tasks and scalp locations, suggesting that these EEG measures can reflect different aspects of cortical functioning.     

Kinetics of G-protein-coupled receptor signals in intact cells

G-protein-coupled receptors (GPCRs) are the largest group of cell surface receptors. They are stimulated by a variety of stimuli and signal to different classes of effectors, including several types of ion channels and second messenger-generating enzymes. Recent technical advances, most importantly in the optical recording with energy transfer techniques--fluorescence and bioluminescence resonance energy transfer, FRET and BRET--, have permitted a detailed kinetic analysis of the individual steps of the signalling chain, ranging from ligand binding to the production of second messengers in intact cells. The transfer of information, which is initiated by ligand binding, triggers a signalling cascade that displays various rate-controlling steps at different levels. This review summarizes recent findings illustrating the speed and the complexity of this signalling system.     

Application of xidiphone in complex of measures for inflammatory periodontal disease prevention

Investigation of basic biochemical parameters of mixed saliva during sugar and urea tests including application of xidiphone has been carried out. Following parameters--pH, concentration of calcium, inorganic phosphate and fluoride--were measured. It was shown that xidiphone was an universal regulator of acid-base state, calcium-phosphorus an calcium-fluoride homeostasis in oral cavity.