BACKGROUND: The PI*S variant is one of the most prevalent mutations within alpha-1 antitrypsin deficiency (AATD). The risk of developing AATD-related lung disease in individuals with the PI*SS genotype is poorly defined despite its substantial prevalence. Our study aimed to characterize this genotype and its risk for lung disease and compare it with the PI*ZZ and PI*SZ genotypes using data from the European Alpha-1 antitrypsin Deficiency Research Collaboration international registry. METHOD: Demographic, clinical, functional, and quality of life (QoL) parameters were assessed to compare the PI*SS characteristics with the PI*SZ and PI*ZZ controls. A propensity score with 1:3 nearest-neighbour matching was performed for the most important confounding variables. RESULTS: The study included 1007 individuals, with PI*SS (n = 56; 5.6%), PI*ZZ (n = 578; 57.4%) and PI*SZ (n = 373; 37.0%). The PI*SS population consisted of 58.9% men, with a mean age of 59.2 years and a mean FEV1(% predicted) of 83.4%. Compared to PI*ZZ individuals they had less frequent lung disease (71.4% vs. 82.2%, p = 0.037), COPD (41.4% vs. 60%, p = 0.002), and emphysema (23.2% vs. 51.9%, p < 0.001) and better preserved lung function, fewer exacerbations, lower level of dyspnoea, and better QoL. In contrast, no significant differences were found in the prevalence of lung diseases between PI*SS and PI*SZ, or lung function parameters, exacerbations, dyspnoea, or QoL. CONCLUSIONS: We found that, as expected, the risk of lung disease associated with the PI*SS genotype is significantly lower compared with PI*ZZ, but does not differ from that observed in PI*SZ individuals, despite having higher serum AAT levels. TRIAL REGISTRATION: www. CLINICALTRIALS: gov (ID: NCT04180319).
- Klíčová slova
- Alpha-1 antitrypsin, Lung disease, PI*SS, Registries,
- MeSH
- alfa-1-antitrypsin * genetika MeSH
- deficit alfa1-antitrypsinu * genetika epidemiologie diagnóza MeSH
- genotyp * MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- plicní nemoci genetika epidemiologie diagnóza MeSH
- registrace MeSH
- rizikové faktory MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Názvy látek
- alfa-1-antitrypsin * MeSH
- SERPINA1 protein, human MeSH Prohlížeč
A novel application of a single stranded (ss) oligonucleotide as an active component of polymeric membrane in an ion-selective electrode (ISE) is described. The original oligonucleotides, oligo(dA)(15), modified by cholesterol, triphenylmethyl and hexadecyl derivatives, were immobilized into poly(vinyl chloride) (PVC) membrane using extraction protocol. In parallel, the adsorption protocol was used to immobilize unmodified oligo(dA)(15) on the PVC membrane based on tridodecylmethyammonium chloride (TDDMA(+)Cl(-)). Immobilization of ss oligonucleotide probe through spacer was more effective for the potentiometric detection of the hybridization between complementary oligonucleotides. It was found that cholesterol-oligo(dA)(15) modified membranes were sensitive toward complementary oligo(dT)(15) in the concentration range 2-80 nM at pH 7. An explanation for the detection mechanism is proposed.
- MeSH
- analýza selhání vybavení MeSH
- biokompatibilní potahované materiály chemie MeSH
- biosenzitivní techniky přístrojové vybavení metody MeSH
- design vybavení MeSH
- DNA sondy chemie genetika MeSH
- elektrochemie přístrojové vybavení metody MeSH
- hybridizace in situ přístrojové vybavení metody MeSH
- oligonukleotidy analýza chemie genetika MeSH
- polyvinylchlorid chemie MeSH
- reprodukovatelnost výsledků MeSH
- senzitivita a specificita MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biokompatibilní potahované materiály MeSH
- DNA sondy MeSH
- oligonukleotidy MeSH
- polyvinylchlorid MeSH
The determination of trace metal contents directly from a solid sample is a trend in modern atomic spectrometry. The aim of this study was to develop an analytical method for the routine determination of Cd in lichens using solid sampling graphite furnace atomic absorption spectrometry (SS-GF-AAS). For the determination of Cd, the temperature program of the graphite furnace was optimized using a mixed matrix modifier (Pd + Mg (NO3)2 + Triton X-100). The limit of detection and the limit of quantification were 0.9 μg/kg and 3 μg/kg, respectively. The analytical method for Cd determination in the plant matrix was verified by the analysis of certified reference materials of lichens, seaweed, and rye grass. The developed procedure was applied to the study of Cd distribution in thalli of Usnea antarctica lichen from James Ross Island, Antarctica. The SS-GF-AAS analytical method is particularly suited for use in environmental studies and plant physiology (the microanalysis of anatomical structures).
- Klíčová slova
- AAS, Cadmium, Lichen, Solid sampling,
- MeSH
- grafit * MeSH
- kadmium * analýza MeSH
- látky znečišťující životní prostředí * analýza MeSH
- lišejníky * chemie MeSH
- monitorování životního prostředí MeSH
- ostrovy MeSH
- spektrofotometrie atomová MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Antarktida MeSH
- ostrovy MeSH
- Názvy látek
- grafit * MeSH
- kadmium * MeSH
- látky znečišťující životní prostředí * MeSH
Utilizing a plasma focus (PF) instrument, magnesium nitride (Mg3 N2 ) thin films were synthesized on stainless steel substrates. Twenty five optimum focus shots at 8 cm distance from the anode tip were used to deposit the films at different angular positions regarded to the anode axis. Scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray diffraction (XRD) analyses were performed to assess the surface morphology and structural characteristics of Mg3 N2 films. Based on AFM images, these films were studied to understand the effect of angular position variation on their surfaces through morphological and fractal parameters. By increasing the angle, we verify that the grain size decreased from 130(0) nm to 75(5) nm and also the mean quadratic surface roughness of the films reduced in its average values from (28.97 ± 3.24) nm to (23.10 ± 1.34) nm. Power spectrum density analysis indicated that films become more self-affine at larger angles. Furthermore, the corrosion behavior of the films was investigated through a potentiodynamic polarization test in H2 SO4 solution. It was found that the ion energy and flux, varying with the angular positions from the anode tip, directly affected the nanostructured roughness and surface morphology of the samples. The electrochemical studies of films show that the uncoated sample presented the lowest corrosion resistance. The highest corrosion resistance was obtained for the sample deposited with 25 optimum shots and at 0° angular position reaching a reduction in the corrosion current density of almost 800 times compared to the pure stainless steel-304 substrate. HIGHLIGHTS: Mg3 N2 /SS films have been deposited at different angles by plasma focus (PF) instruments. The effect of angular position on the surface microtexture, morphological parameters, and corrosion features of the films was studied. The RBS measurement and X-ray diffraction are utilized to identify the crystalline phases and thickness of films.
- Klíčová slova
- corrosion, magnesium nitride films, microstructure, morphology, plasma focus, stainless steel,
- Publikační typ
- časopisecké články MeSH
Isoxazole is a five-membered heterocycle that is widely used in drug discovery endeavors. Here, we report the design, synthesis, and structural and biological characterization of SS-208, a novel HDAC6-selective inhibitor containing the isoxazole-3-hydroxamate moiety as a zinc-binding group as well as a hydrophobic linker. A crystal structure of the Danio rerio HDAC6/SS-208 complex reveals a bidentate coordination of the active-site zinc ion that differs from the preferred monodentate coordination observed for HDAC6 complexes with phenylhydroxamate-based inhibitors. While SS-208 has minimal effects on the viability of murine SM1 melanoma cells in vitro, it significantly reduced in vivo tumor growth in a murine SM1 syngeneic melanoma mouse model. These findings suggest that the antitumor activity of SS-208 is mainly mediated by immune-related antitumor activity as evidenced by the increased infiltration of CD8+ and NK+ T cells and the enhanced ratio of M1 and M2 macrophages in the tumor microenvironment.
- MeSH
- CD8-pozitivní T-lymfocyty cytologie MeSH
- dánio pruhované MeSH
- histondeacetylasa 6 antagonisté a inhibitory MeSH
- inhibitory histondeacetylas chemie farmakologie MeSH
- isoxazoly chemie farmakologie MeSH
- katalytická doména MeSH
- kyseliny hydroxamové chemie farmakologie MeSH
- lidé MeSH
- makrofágy cytologie MeSH
- melanom farmakoterapie MeSH
- mikrozomy chemie MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- NKT buňky cytologie MeSH
- objevování léků MeSH
- transplantace izogenní MeSH
- zinek chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- HDAC6 protein, human MeSH Prohlížeč
- Hdac6 protein, mouse MeSH Prohlížeč
- histondeacetylasa 6 MeSH
- inhibitory histondeacetylas MeSH
- isoxazoly MeSH
- kyseliny hydroxamové MeSH
- zinek MeSH
- MeSH
- antisérum farmakologie MeSH
- chemická precipitace MeSH
- druhová specificita * MeSH
- genotyp MeSH
- hemaglutinační testy MeSH
- heterozygot MeSH
- homozygot MeSH
- imunodifuze MeSH
- koně MeSH
- králíci MeSH
- krevní proteiny analýza MeSH
- morčata MeSH
- myši MeSH
- prasata MeSH
- skot MeSH
- testování histokompatibility MeSH
- zkřížené reakce * MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- morčata MeSH
- myši MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antisérum MeSH
- krevní proteiny MeSH
- MeSH
- dietní proteiny aplikace a dávkování MeSH
- dietní sacharidy aplikace a dávkování MeSH
- dietní tuky aplikace a dávkování MeSH
- dítě MeSH
- dospělí MeSH
- fyziologie výživy * MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- novorozenec MeSH
- nutriční nároky MeSH
- předškolní dítě MeSH
- senioři MeSH
- těhotenství MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- senioři MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Československo MeSH
- Názvy látek
- dietní proteiny MeSH
- dietní sacharidy MeSH
- dietní tuky MeSH
- MeSH
- dějiny 20. století MeSH
- řízení veřejného zdraví dějiny MeSH
- Check Tag
- dějiny 20. století MeSH
- Publikační typ
- biografie MeSH
- časopisecké články MeSH
- historické články MeSH
- Geografické názvy
- Československo MeSH
- O autorovi
- Vrabelová, R
- MeSH
- dějiny lékařství MeSH
- řízení veřejného zdraví MeSH
- státní lékařství MeSH
- Publikační typ
- biografie MeSH
- časopisecké články MeSH
- historické články MeSH
- Geografické názvy
- Československo MeSH
- O autorovi
- Vrábelová, R
- MeSH
- aminokyseliny MeSH
- dietní sacharidy MeSH
- dietní tuky MeSH
- fyziologie výživy * MeSH
- lidé MeSH
- nutriční nároky MeSH
- vitaminy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Československo MeSH
- Názvy látek
- aminokyseliny MeSH
- dietní sacharidy MeSH
- dietní tuky MeSH
- vitaminy MeSH
