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INTRODUCTION: Inhalation of nanomaterials may induce inflammation in the lung which if left unresolved can manifest in pulmonary fibrosis. In these processes, alveolar macrophages have an essential role and timely modulation of the macrophage phenotype is imperative in the onset and resolution of inflammatory responses. This study aimed to investigate, the immunomodulating properties of two industrially relevant high aspect ratio nanomaterials, namely nanocellulose and multiwalled carbon nanotubes (MWCNT), in an alveolar macrophage model. METHODS: MH-S alveolar macrophages were exposed at air-liquid interface to cellulose nanocrystals (CNC), cellulose nanofibers (CNF) and two MWCNT (NM-400 and NM-401). Following exposure, changes in macrophage polarization markers and secretion of inflammatory cytokines were analyzed. Furthermore, the potential contribution of epigenetic regulation in nanomaterial-induced macrophage polarization was investigated by assessing changes in epigenetic regulatory enzymes, miRNAs, and rRNA modifications. RESULTS: Our data illustrate that the investigated nanomaterials trigger phenotypic changes in alveolar macrophages, where CNF exposure leads to enhanced M1 phenotype and MWCNT promotes M2 phenotype. Furthermore, MWCNT exposure induced more prominent epigenetic regulatory events with changes in the expression of histone modification and DNA methylation enzymes as well as in miRNA transcript levels. MWCNT-enhanced changes in the macrophage phenotype were correlated with prominent downregulation of the histone methyltransferases Kmt2a and Smyd5 and histone deacetylases Hdac4, Hdac9 and Sirt1 indicating that both histone methylation and acetylation events may be critical in the Th2 responses to MWCNT. Furthermore, MWCNT as well as CNF exposure led to altered miRNA levels, where miR-155-5p, miR-16-1-3p, miR-25-3p, and miR-27a-5p were significantly regulated by both materials. PANTHER pathway analysis of the identified miRNA targets showed that both materials affected growth factor (PDGF, EGF and FGF), Ras/MAPKs, CCKR, GnRH-R, integrin, and endothelin signaling pathways. These pathways are important in inflammation or in the activation, polarization, migration, and regulation of phagocytic capacity of macrophages. In addition, pathways involved in interleukin, WNT and TGFB signaling were highly enriched following MWCNT exposure. CONCLUSION: Together, these data support the importance of macrophage phenotypic changes in the onset and resolution of inflammation and identify epigenetic patterns in macrophages which may be critical in nanomaterial-induced inflammation and fibrosis.
Smart materials of biological origin are attracting a lot of attention nowadays, especially as catalysts, carriers or adsorbents. Among them, magnetically modified biomaterials are especially important due to their response to external magnetic field. This report demonstrates that naturally occurring micrometer sized, high aspect ratio material (native and autoclaved Leptothrix sp. sheaths) efficiently bind synthetically prepared magnetite and maghemite nanoparticles and their aggregates. Magnetic modification of Leptothrix sheaths enables to prepare a promising material for advanced biotechnology and environmental technology applications. The prepared magnetically responsive sheaths were tested as inexpensive adsorbent for crystal violet removal from aqueous solutions. The observed maximum adsorption capacity was 243.1mg of dye per 1g of adsorbent.
- MeSH
- genciánová violeť chemie MeSH
- Leptothrix chemie MeSH
- magnetické nanočástice chemie MeSH
- Publikační typ
- časopisecké články MeSH
Pre zachovanie optimálneho zdravia je potrebná optimálna hladina každého antioxidanta. Kombinovaný efekt neenzymatickej ochrany (ferric reducing ability of plasma - FRAP) je indexom schopnosti odolávať oxidačnému poškodeniu. Plazmatické hladiny vitamínov C, E, A, β-karotén ako aj molámy pomer vitamín E/cholesterol a vitamín C/vitamín E sú signifikantne vyššie v alternatívnej nutričnej skupine (vegetariáni) v porovnaní s kontrolnou skupinou tradičnej výživy. Nadprahové hodnoty esenciálnych antioxidantov (z potravy) znamenitú redukované riziko voľnoradikálových ochorení. Priemerné hodnoty vitamínu C, vitamínu E, vitamínu E/cholesterol, vitamínu C/vitamínu E, vitamínu A a β-kuroténu V skupine vegetariánov sú nadprahové s vysokým percentom individuálnych hodnôt nad limitom (92 % vs 42 % - vitamín C, 88 % vs 50 % - vitamín E/cholesterol, 100 % vs 79 % - vitamín C/vitamín E, 75 % vs 38 % - vitamín A, 67 % vs 17 % - β-karotén). V kontrolnej skupine má nadprahovú hodnotu len vitamín C/vitamín E. Typickým rozdielom alternatívneho stravovania v porovnaní s tradičným je vyššia konzumácia ovocia a zeleniny (vyšší príjem vitamínu C a β-karoténu), ďalej konzumácia celozmných produktov, klíčkov, semien a netradičných rastlinných tukov (tiež vyšší príjem vitamínov E a A). Hladiny exogénnych antioxidantov u zdravej populácie s normálnou absorpciou živín sú plne závislé na skladbe potravy. Hodnoty FRAP sú vyrovnané pre obidve sledované skupiny. Podiel aktivity jednotlivých antioxidantov na celkovej hodnote FRAP je vyšší pre vitamín C a vitamín E u vegetariánov a pre kyselinu močovú v kontrolnej skupine. V prípade celkových bielkovín podiel aktivity je rovnaký vo vegetariánskej aj kontrolnej skupine.
Optimal level of each antioxidant is required for maintenance of optimal health. Combined antioxidant effect of nonenzymatic defenses (ferric reducing ability of plasma - FRAP) is useful as index of ability to resist oxidative damage. Plasma values of vitamins C, E, A, β-carotene as well as molar ratios vitamin E/cholesterol and vitamin C/vitamin E are significantly higher in alternative nutrition group (vegetarians) vs. subjects on traditional nutrition (control group). Overthreshold plasma values of essential antioxidants (from food) mean a reduced risk of freeradical diseases. Average values of vitamin C, vitamin E, vitamin E/cholesterol, vitamin C/vitamin E, vitamin A and β-carotene in vegetarian group are overthreshold with high percent of individual values over limit (92 % vs. 42 % - vitamin C, 88 % vs. 50 % - vitamin E/cholesterol, 100 % vs. 79 % - vitamin C/vitamin E, 75 % vs. 38 % - vitamin A, 67 % vs. 17 % - β-carotene). In control group, overthreshold in only ratio vitamin C/vitamin E. A typical difference of alternative nutrition in comparison to traditional nutrition is higher consumption of fruit and vegetables (higher intake of vitamin C and β-carotene), further consumption of whole grain products, sprouts, seeds and nontraditional plant fats (also higher intake of vitamin E and A). Levels of exogenous antioxidants in healthy population with normal nutrient absorption are fully influenced by food composition. The values of FRAP are equal in both investigated groups. Activity contribution of individual antioxidants to total FRAP is higher for vitamins C and E in vegetarian group and for uric acid in control group. In case of total proteins, the activity contribution is similar in vegetarian group as well as in control group.
- MeSH
- antidepresiva aplikace a dávkování terapeutické užití MeSH
- dětská psychiatrie MeSH
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- selektivní inhibitory zpětného vychytávání serotoninu terapeutické užití MeSH
- sertralin aplikace a dávkování farmakologie škodlivé účinky MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH
Autoři analyzují příčiny a mechanismus vzniku úrazů v závislosti na pořadí výskytu,pohlaví a věku pacientů .Za 24 měsíců ošetřili 331 dospělých pacientů a 31 dětí s poraněnímobličejového skeletu. Pro zlomeninu kostí horní a střední třetiny obličeje bylo léčeno 25 pacientů(7,5 %). Izolovanou zlomeninu nosních kůstek diagnostikovali u 276 dospělých pacientů (83 %) a 31dětí. U 31 dospělých pacientů (10 %) šlo o zlomeninu otevřenou a u 28 pacientů (9 %) byla repozicedislokovaných nosních kůstek provedena v celkové anestezii. Dále ošetřili 30 pacientů (9 %) s poly-traumatem a zlomeninou kostí horní a střední obličejové etáže. Nejčastější příčinou poraněníobličejového skeletu bylo násilí jiné osoby - kriminální úraz u 153 pacientů (46 %), podíl mužů naporaněních horní a střední třetiny obličeje byl 132 (87 %) s maximem výskytu mezi 2.-3. deceniem.Druhou nejčastější příčinou úrazů obličeje byly pády 89 pacientů (27 %), při stejném zastoupeníobou pohlaví a s nejvyšším věkovým průměrem. Sportovní úrazy se vyskytovaly u 44 pacientů(13 %), k dopravním úrazům došlo u 40 pacientů (12 %). Tato poranění svým rozsahem i závažnostípatřila k nejtěžším, protože u většiny z nich šlo často o polytrauma.
The authors analyze the causes and mechanism of contraction of injuries in relation to the frequency of prevalence, sex and age of the patients. In the course of 24 months they treated 331 adult patients and 31 children with injuries of the facial skeleton. On account of fractures of the upper and medial third of the face 25 patients (7.5 % were treated. Isolated fractures of the nasal bones were diagnosed in 276 adult patients (83 %) and in 31 children. In 31 adult patients (10 %) an open fracture was involved and in 28 patients (9 %) reposition of the dislocated nasal bones was made under general anaesthesia. The authors treated also 30 patients (9 %) with multiple injuries and fractures of bones in the upper and medial portion of the face. The most frequent cause of injuries of the facial skeleton was violence caused by another person in 153 patients (46 %), the ratio of men with injuries of the upper and medial third of the face was 132 (87 %) with a maximum incidence between the second and third decade. The second most frequent cause of facial injuries were falls - 89 patients (27 %), both sexes being equally represented, the mean age being high. Sports injuries were recorded in 44 patients (13 %), transport injuries were recorded in 40 patients (12 %). The latter injuries were as to their extent and serious character the most severe ones as in the majority multiple injuries were involved.
Závažnost koronárních lézí vždy představovala významný aspekt péče o pacienty během koronarografického vyšetření. Je prokázáno, že léčba vedená na základě hodnot frakční průtokové rezervy (fractional flow reserve, FFR) má pozitivní vliv na klinický výsledný stav pacienta. Zavádění FFR do klinické praxe v celosvětovém měřítku nicméně zpomalily závažné technické nedostatky. V poslední době byla představena a v klinickém výzkumu ověřována jiná kritéria, jako například kvantitativní poměr průtoků (quantitative flow ratio, QFR). Podle jedné studie používající výpočetní mechaniku tekutin a plynů koreluje QFR s hodnotami FFR a ve srovnání s jinými metodami šetří čas i peníze. QFR představuje novou angiografickou metodu, která pomocí moderního softwaru provádí trojrozměrnou rekonstrukci cév a vytváří modely průtoku. Jedná se tedy o technicky vyspělou metodu a o moderní, účinný a praktický nástroj pro hodnocení koronárních lézí. Cílem tohoto přehledu bylo prozkoumat oblasti případného využití QFR v klinické praxi.
The severity of coronary lesions (CL) has always been an important aspect of patient care during coronary angiography. Fractional flow reserve (FFR)-guided coronary treatments have been shown to have a positive influence on clinical outcomes. However, significant technical flaws in clinical practice have slowed global adoption of FFR. Other indices, such as the quantitative flow ratio (QFR), have recently been created and tested in clinical research. According to a computational fluid dynamics study, QFR has a good correlation with FFR values and saves time and money compared to other methods. QFR is a new angiographic technique that uses modern software to reconstruct three-dimensional vessels and calculate flow models. Modern, effective and usable tool for CL due to significant technical benefits. We aimed to analyze the application areas of the QFR and its potential clinical application in this review.
Léčba bazálním inzulínem v kombinaci s perorálními antidiabetiky již dlouhodobě patří k ověřeným postupům v kompenzaci diabetes mellitus 2. typu. Dalším krokem v intenzifikaci léčby podle doporučení odborných společností může být buď přidání krátkodobě působícího analoga v režimu bazál-plus či bazál-bolus, nebo nová možnost - kombinace s agonisty GLP-1 (glucagon-like peptide 1). Fixní kombinace liraglutid/degludek kombinuje dlouhodobě působícího agonistu GLP-1 liraglutid s dlouhodobě působícím inzulinovým analogem degludek. Inzulin degludek dobře ovlivní glykémii nalačno a účinek liraglutidu spočívá ve snížení glykémie nalačno i postprandiálně bez rizika hypoglykemických příhod a v redukci hmotnosti. Liraglutid ve studii LEADER snižoval kardiovaskulární riziko podle tříbodového MACE (major adverse cardiovascular events), složeného z kardiovaskulárního úmrtí, nefatálního infarktu myokardu a nefatální cévní mozkové příhody, a byl signifikantně účinný také ve snížení rizika mikrovaskulárních komplikací. Fixní přípravek inzulin degludek/liraglutid (Xultophy) s aplikací jedenkrát denně byl hodnocen po stránce účinnosti a bezpečnosti v programu studií DUAL. Byla prokázána jeho superiorita ve srovnání s inzulinem glargin U100. Nezbytnou součástí léčby je i správná titrace, která byla posuzována ve studii DUAL VI.
The therapy of basal insulin in combination with oral antidiabetic agents has its position for a long time among attested procedures in the compensation of type 2 diabetes mellitus. A further step in the intensification of therapy in accord with the recommendation of specialized associations can either be addition of a short-term analogue in a regimen of basal plus or basal-bolus, or a new possibility is in combination with glucagon-like peptide 1 (GLP-1) receptor agonists. A fixed-ratio combination of liraglutide/degludec combines the long-term acting of GLP-1 receptor agonist liraglutide with the longterm action of the insulin analogue insulin degludec. Insulin degludec has a good influence on fasting plasma glucose and liraglutide decreases fasting plasma glucose and postprandial plasma glucose without the risk of hypoglycemic events and at the same time reduces weight loss. In the LEADER trial liraglutide reduced cardiovascular risk according to the 3-point MACE (major adverse cardiovascular events) composed of cardiovascular death, nonfatal myocardial infarction and nonfatal strokes and it was significantly effective in reducing the risks of microvascular complications. The fixed-ratio preparation of insulin degludec/liraglutide (Xultophy) applied once a day was assessed from the aspect of effectiveness and safety in the program of DUAL study, namely in DUAL V trial, its superiority was proven in comparison with glargin U100. An essential integral part of the therapy is also correct titration which was appraised in DUAL VI trial.
- Klíčová slova
- inzulin degludek, studie DUAL, studie LEADER, Xultophy,
- MeSH
- diabetes mellitus 2. typu * farmakoterapie MeSH
- dlouhodobě působící inzulin * farmakologie škodlivé účinky terapeutické užití MeSH
- fixní kombinace léků MeSH
- glukagonu podobný peptid 1 analogy a deriváty MeSH
- kardiovaskulární nemoci mortalita prevence a kontrola MeSH
- klinické zkoušky, fáze III jako téma MeSH
- lidé MeSH
- liraglutid * farmakologie škodlivé účinky terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
The aim of this study was a contemporaneous measurement of plasma cells proliferative and apoptotic activity in patients examined at the time of multiple myeloma (MM) diagnosis before initiation of chemotherapy, focussed on the following aspects: determination of prognostic significance of plasma cell propidium iodide (PC-PI) and annexin-V FITC (PC-AI) indices; optimal cut off of PC-PI and PC-AI with regard to overall survival; calculation of summary kinetic index of plasma cells (PC-PI/AI ratio) for evaluation of its prognostic importance; determination of an index (out of PC-PI, PC-AI and PC-PI/AI) showing the closest relation to prognosis of multiple myeloma. The analyzed 122 patients fulfilling SWOG multiple myeloma criteria were treated by conventional chemotherapy. Plasma cell proliferative activity was measured by means of PC-PI examined by flow cytometry using a DNA/CD138 double staining technique. For detection of plasma cells entering apoptosis (PC-AI), flow-cytometry method with annexin-V FITC and MoAb CD138 was used. The PC-PI median in 122 patients was 2.6(0.4-4.8)%. The sequence prognostic analysis showed that the optimal PC-PI cut off was 2.9% and displayed a significant relationship with overall survival (OS) (p=0.031). The group of 94 patients had PC-AI median of 5.0(1.4-24.5)%. The best statistical significance of the rate of apoptosis related to overall survival was found at cut off value of 4.4% (p=0.022). The median of overall kinetic index of plasma cells (PC-PI/AI) examined in 94 MM patients was 0.5(0.05-2.60) and the overall kinetic index was found to display a very good relationship to OS at the cut off value of 0.71 (p=0.032). All the three indices expressing various aspects of kinetics of plasma cells allow the stratification of patients into two prognostically different groups with statistically significantly different medians of overall survival: good risk - OS still undeterminable at the time of analysis; bad risk - M: OS was for PC-PI 17 months, for PC-AI 23 months and for PC-PI/AI 16 months. The ratio of both indices, i.e. PC- PI/AI, however did not bring any further contribution to overall survival/prognosis evaluation, when compared with single PC-PI and PC-AI. Results of present study indicates that the evaluation of both proliferation and apoptotic activities of plasma cells is important for prognosis thus extending possibilities of initial stratification of MMpatients into groups with different prognostic risk.
- MeSH
- annexin A5 MeSH
- apoptóza * MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom * krev mortalita patologie MeSH
- plazmatické buňky * patologie MeSH
- prognóza MeSH
- proliferace buněk MeSH
- propidium MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
The family environment is associated with religiosity and spirituality as well as many aspects of adolescent lives, including their health behaviour. Therefore, the aim of this study was to assess family environment associations with adolescent religious attendance (RA), i.e., weekly participation in religious services, and spirituality in a highly secular country. A nationally representative sample (n = 4182, 14.4 ± 1.1 years, 48.6% boys) of Czech adolescents participated in the 2014 Health Behaviour in School-aged Children cross-sectional study. RA, spirituality and the family environment, i.e., family communication, perceived emotional support, and parental monitoring, were measured. Higher adolescent RA was associated with lower self-reported easiness of communication with mother (odds ratio (OR) = 0.68; 99% confidence interval (99% CI) = 0.47-0.99; p < 0.01). In contrast, spiritual respondents were more likely to report both easier communication with their father (OR per standard deviation (SD) change = 1.12, 99% CI 1.02-1.23; p < 0.01) and mother (OR per SD change = 1.38 (1.23-1.55); p < 0.001) and higher perceived emotional support (OR per SD change = 1.73 (1.55-1.92); p < 0.001). Parents of respondents who attended religious services at least once a week, as well as parents of spiritual respondents, were generally more likely to monitor adolescent behaviour. Thus, this study provides information for parents, mental health workers, and pastoral carers. Further research should assess the association of a lower easiness of family communication with dissonances in adolescent-parent religiosity/spirituality and with higher parental monitoring.
- MeSH
- charakteristiky rodiny * MeSH
- chování mladistvých * MeSH
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- náboženství * MeSH
- odds ratio MeSH
- průřezové studie MeSH
- rodinné vztahy * MeSH
- spiritualita * MeSH
- zpráva o sobě MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH