Abstract Delivery of active protein especially enzyme is one of the major therapeutic challenge. Replacing or substituted invalid/improper acting protein offer fast and effective treatment of ...disease. Herein, we describe the synthesis and properties of biotinylated peptidomimetics consisting of oxoacid—modified 2,3, l -diaminopropionic acid residues with guanidine groups on its side chains. Electrophoretic analysis showed that the obtained compounds interact with FITC-labeled streptavidin or a streptavidin-β-galactosidase hybrid in an efficient manner. Complexes formed by the abovementioned molecules are able to cross the cell membranes of cancer or healthy cells and show promising compatibility with live cells. Analysis of β-galactosidase activity inside the cells revealed surprisingly high levels of active enzyme in complex-treated cells compared to controls. This observation was confirmed by immunochemical studies in which the presence of β-galactosidase was detected in the membrane and vesicles of the cells.
Antimicrobial peptides (AMPs) exhibit a wide spectrum of actions, ranging from a direct bactericidal effect to multifunctional activities as immune effector molecules. The aim of this study was to ...examine the anti-inflammatory properties of a DAL-PEG-DK5 conjugate composed of a lysine-rich derivative of amphibian temporin-1CEb (DK5) and dalargin (DAL), the synthetic Leu-enkephalin analogue. Detailed study of the endotoxin-neutralizing activity of the peptide revealed that DAL-PEG-DK5 interacts with LPS and the LPS binding protein (LBP). Moreover, DAL-PEG-DK5 prevented dimerization of TLR4 at the macrophage surface upon LPS stimulation. This inhibited activation of the NF-κB signaling pathway and markedly reduced pro-inflammatory cytokine production. Finally, we showed that aggregation of DAL-PEG-DK5 into amyloid-like structures induced by LPS neutralized the endotoxin proinflammatory activity. Consequently, DAL-PEG-DK5 reduced morbidity and mortality in vivo, in a mouse model of endotoxin-induced septic shock. Collectively, the data suggest that DAL-PEG-DK5 is a promising therapeutic compound for sepsis.
Dynamic modelling has considerably improved our understanding of complex molecular mechanisms. Ordinary differential equations (ODEs) are the most detailed and popular approach to modelling the ...dynamics of molecular systems. However, their application in signalling networks, characterised by multi-state molecular complexes, can be prohibitive. Contemporary modelling methods, such as rule- based (RB) modelling, have addressed these issues. The advantages of RB modelling over ODEs have been presented and discussed in numerous reviews. In this study, we conduct a direct comparison of the time courses of a molecular system founded on the same reaction network but encoded in the two frameworks. To make such a comparison, a set of reactions that underlie an ODE model was manually encoded in the Kappa language, one of the RB implementations. A comparison of the models was performed at the level of model specification and dynamics, acquired through model simulations. In line with previous reports, we confirm that the Kappa model recapitulates the general dynamics of its ODE counterpart with minor differences. These occur when molecules have multiple sites binding the same interactor. Furthermore, activation of these molecules in the RB model is slower than in the ODE one. As reported for other molecular systems, we find that, also for the DARPP-32 reaction network, the RB representation offers a more expressive and flexible syntax that facilitates access to fine details of the model, easing model reuse. In parallel with these analyses, we report a refactored model of the DARPP-32 interaction network that can serve as a canvas for the development of more complex dynamic models to study this important molecular system.
•Natural radionuclides content in building materials added with NORM.•Radon exhalation in concrete added with NORM.•Intercomparison of radon exhalation rate results.•Effect of the concrete ...microstructure on radon exhalation rate.
This paper contains preliminary results of a study on the physical and radiological characterization of concrete samples containing NORM. The natural radionuclides content in term of 226Ra, 228Ra, 232Th, 40K and the radon exhalation rate of the samples were determined. Two series of samples of concrete were prepared: samples belonging to both series were made of the same basic components (Portland cement CEM I 42,5R as binder, aggregate and plasticizer) but different amount of NORM residues and mineral additives were used.
The concrete samples were characterize in term of absolute density, permeability, total and open porosity. The radiological content was evaluated by using gamma spectrometry and the radon exhalation rate measurements were performed using the dynamic method. Moreover, the Activity Concentration Index (I), introduced by the 2013/59/Euratom Directive, has been used in order to evaluate if concrete samples could exceed the reference level for effective dose due to gamma radiation in building materials.
Liquid scintillation counting (LSC) is a measuring technique, broadly applied in environmental monitoring of radionuclides. One of the possible applications of LSC is the measurement of radon and ...thoron decay products. But this method is suitable only for grab sampling. For long-term measurements a different technique can be applied-monitors of potential alpha energy concentration (PAEC) with thermoluminescent detectors (TLD). In these devices, called Alfa-2000 sampling probe, TL detectors (CaSO4:Dy) are applied for alpha particles counting. Three independent heads are placed over the membrane filter in a dust sampler's microcyclone. Such solution enables simultaneous measurements of PAEC and dust content. Moreover, the information which is stored in TLD chips is the energy of alpha particles, not the number of counted particles. Therefore, the readout of TL detector shows directly potential alpha energy, with no dependence on equilibrium factor, etc. This technique, which had been used only for radon decay products measurements, was modified by author to allow simultaneous measurements of radon and thoron PAEC. The LSC method can be used for calibration of portable radon decay products monitors. The LSC method has the advantage to be an absolute one, the TLD method to measure directly the (dose relevant) deposited energy.
The main goal of the research presented was to design and construct a device, enables estimation of the diffusion time and diffusion length for radon in core samples collected from the geological ...layers of Upper Silesian Coal Basin (USCB). Another goal will be investigations of the advection of
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Rn with other gases like carbon dioxide or methane, occurring in the Carboniferous strata in USCB. This knowledge will support the precision of the assessment of radon hazard in working environment. Moreover, it should give an answer to some questions, related to the radon migration issues—if the results of measurements of the transport of radon with other gases in the strata could be applied for the prediction of geodynamic phenomena in the mining areas, like tremors and outbursts. The study was focused on the flow measurements of the following gases: radon, carbon dioxide, nitrogen and their mixtures, as the use of methane was excluded due to potential hazard of explosion. In this article results of measurements of diffusive migration are presented: radon itself and simultaneous migration of radon, nitrogen and carbon dioxide. For this purpose a special device was designed and constructed. This device consists of the container for the sample of coal, mineral or rock and two reservoirs—the inlet and outlet one. The gas (e.g. air or carbon dioxide) with radon is introduced into inlet reservoir, while the content of marker gases and radon is monitored in the outlet reservoir. The preliminary experiments were also performed and are presented in this paper. In the literature, there are only rare results of such investigations, while our previous research in USCB region showed some correlation between sudden changes of radon level and geodynamic events. Therefore, the results of the investigations presented in this study are expected to contribute to the improvement of the models of these phenomena. The future work planned will be aimed at investigations of advective flow of radon with various carrier gases.
The article presents the advantages of the radon chamber with volume of 17 m3, that belongs to Silesian Centre for Environmental Radioactivity and its applicability for calibration of equipment ...designed to measure the radon concentration and its short-lived decay products. The chamber can be operated under controlled conditions in the range from -20 to 60°C and relative humidity from 20 to 90%. There is also discussed the influence of aerosol concentration and their size distribution on the calibration results. When calibrating the measuring devices in an atmosphere with a large contribution of ultrafine particles that are defined as particles with diameter <0.1 μm, their sensitivity may decrease by tens of percent.
We report the synthesis and enzymatic studies on a new proteinase 3 intermolecular quenched substrate with enhanced selectivity over neutrophil elastase. Using combinatorial chemistry methods, we ...were able to synthesize the hexapeptide library with the general formula ABZ-Tyr-Tyr-Abu-X1′-X2′-X3′-Tyr(3-NO2)-NH2 using the mix and split method. The iterative deconvolution of such a library allowed us to obtain the sequence ABZ-Tyr-Tyr-Abu-Asn-Glu-Pro-Tyr(3-NO2)-NH2 with a high specificity constant (kcat/KM=1534×103M−1s−1) and superior selectivity over neutrophil elastase and other neutrophil-derived serine proteases. Moreover, using the obtained substrate, we were able to detect a picomolar concentration of proteinase 3 (PR3). Incubation of the above-mentioned substrate with neutrophil lysate resulted in a strong fluorescent signal that was significantly reduced in the presence of a PR3 selective inhibitor.
Purpose
To evaluate the conjunctival sac flora before and after intravitreal injection (IVI) in eyes with no prophylactic antibiotic use.
Methods
37 eyes of 37 patients not using systemic or local ...antibiotics for at least 30 days were included. Microbiological culture from conjunctiva sac to nutrient media was taken twice: before IVI and before any topical medications were given and 30 minutes after anty‐VEGF IVI. Topical antibiotics were not used neither before, nor after IVI. Shortly before IVI conjunctival sac was rinsed with 5% povidone‐iodine (PVI). Control group constituted eyes not treated with IVI of the same patients.
Results
Negative microbiological cultures before and after IVI were noted in the studied group in 15 patients (40.5%) and in 9 control eyes (24.3%). Coagulase‐negative Staphylococci (CNS) were cultured in 13 eyes (35.1%) before IVI and in 8 eyes (21.6%) after IVI. In 3 eyes (8.1%) Staphylococcus aureus was shown before IVI, with subsequent negative cultures. In the control group CNS was shown in 14 eyes (37.8%) before IVI and in 7% (18.9%) after IVI. Microbiological flora was identical in studied and control groups in 14 cases (37.8%). There was no case of post‐IVI endophthalmitis.
Conclusions
About 50% of cultures were negative, in 35% ‐ CNS, and in 15% ‐ other bacteria were cultured, including Staphylococcus aureus in 8%. The number of negative cultures after IVI (the use of PVI) was higher than before IVI, and all Staphylococcus aureus were eliminated. The eye antisepsis based on PVI in IVI is an effective and efficient prophylaxis method.
Purpose
To evaluate the conjunctival sac flora before and after intravitreal injection (IVI) in eyes with no prophylactic antibiotic use.
Methods
37 eyes of 37 patients not using systemic or local ...antibiotics for at least 30 days were included. Microbiological culture from conjunctiva sac to nutrient media was taken twice: before IVI and before any topical medications were given and 30 minutes after anty‐VEGF IVI. Topical antibiotics were not used neither before, nor after IVI. Shortly before IVI conjunctival sac was rinsed with 5% povidone‐iodine (PVI). Control group constituted eyes not treated with IVI of the same patients.
Results
Negative microbiological cultures before and after IVI were noted in the studied group in 15 patients (40.5%) and in 9 control eyes (24.3%). Coagulase‐negative Staphylococci (CNS) were cultured in 13 eyes (35.1%) before IVI and in 8 eyes (21.6%) after IVI. In 3 eyes (8.1%) Staphylococcus aureus was shown before IVI, with subsequent negative cultures. In the control group CNS was shown in 14 eyes (37.8%) before IVI and in 7% (18.9%) after IVI. Microbiological flora was identical in studied and control groups in 14 cases (37.8%). There was no case of post‐IVI endophthalmitis.
Conclusions
About 50% of cultures were negative, in 35% – CNS, and in 15% – other bacteria were cultured, including Staphylococcus aureus in 8%. The number of negative cultures after IVI (the use of PVI) was higher than before IVI, and all Staphylococcus aureus were eliminated. The eye antisepsis based on PVI in IVI is an effective and efficient prophylaxis method.
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