Non-alcoholic fatty liver disease (NAFLD) is a general term for fatty liver disease not caused by viruses or alcohol. Fibrotic hepatitis, cirrhosis, and hepatocellular carcinoma can develop. The recent increase in NAFLD incidence worldwide has stimulated drug development efforts. However, there is still no approved treatment. This may be due in part to the fact that non-alcoholic steatohepatitis (NASH) pathogenesis is very complex, and its mechanisms are not well understood. Studies with animals are very important for understanding the pathogenesis. Due to the close association between the establishment of human NASH pathology and metabolic syndrome, several animal models have been reported, especially in the context of overnutrition. In this study, we investigated the induction of NASH-like pathology by enhancing cholesterol absorption through treatment with hydroxypropyl-beta-cyclodextrin (CDX). Female Sprague-Dawley rats were fed a normal diet with normal water (control group); a high-fat (60 kcal%), cholesterol (1.25 %), and cholic acid (0.5 %) diet with normal water (HFCC group); or HFCC diet with 2 % CDX water (HFCC+CDX group) for 16 weeks. Compared to the control group, the HFCC and HFCC+CDX groups showed increased blood levels of total cholesterol, aspartate aminotransferase, and alanine aminotransferase. At autopsy, parameters related to hepatic lipid synthesis, oxidative stress, inflammation, and fibrosis were elevated, suggesting the development of NAFLD/NASH. Elevated levels of endoplasmic reticulum stress-related genes were evident in the HFCC+CDX group. In the novel rat model, excessive cholesterol intake and accelerated absorption contributed to NAFLD/NASH pathogenesis.
- MeSH
- cholesterol MeSH
- dieta s vysokým obsahem tuků škodlivé účinky MeSH
- hydroxypropyl beta cyklodextrin metabolismus terapeutické užití MeSH
- hypercholesterolemie * metabolismus MeSH
- hyperlipidemie * MeSH
- játra metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- nealkoholová steatóza jater * chemicky indukované MeSH
- potkani Sprague-Dawley MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Svalová relaxancia jsou nejčastějšími léčivy způsobujícími alergické reakce v perioperačním období. Vzhledem k intravenóznímu podání léčiv během celkové anestezie mohou být tyto reakce potenciálně život ohrožující. V kazuistice popisujeme případ rokuroniem indukovaného anafylaktického šoku u 26leté ženy s podezřením na mimoděložní těhotenství úspěšně léčeného podáním sugammadexu.
Muscle relaxants are the most common cause of allergic reactions during the perioperative period. This reaction could be potentially life-threatening because of the intravenous route of administration of the drugs used for general anesthesia. We describe a case of rocuronium-induced anaphylactic shock in a 26-years-old woman with suspected extrauterine pregnancy successfully treated with sugammadex.
- MeSH
- anafylaxe * etiologie farmakoterapie MeSH
- dospělí MeSH
- lidé MeSH
- mimoděložní těhotenství chirurgie MeSH
- rokuronium * škodlivé účinky MeSH
- sugammadex aplikace a dávkování terapeutické užití MeSH
- těhotenství MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Svalová relaxancia se používají při téměř dvou třetinách anestezií. V případě jejich použití je důležitá následná důsledná reverze nervosvalové blokády, neboť pooperační reziduální kurarizace zvyšuje pooperační morbiditu. K reverzi svalové blokády lze využít sugammadex, který se vyznačuje velmi dobrou účinností a výhodným bezpečnostním profilem; největší přínos z jeho použití byl dokumentován u nemocných ve věku > 65 let, se skóre ASA ≥ III či s indexem tělesné hmotnosti > 35 a u pacientů podstupujících laparoskopický výkon. Podání sugammadexu brání vzniku pooperačních komplikací, zvyšuje bezpečnost pro pacienta a v současné době lze sugammadex považovat za standard, jehož využití by mělo být zvažováno u výrazně většího spektra pacientů, než tomu bylo dosud.
Muscle relaxants are used in almost two-thirds of anaesthesias. In case they are used, subsequent adequate reversal of neuromuscular blockade is crucial, as post- operative residual curarisation increases postoperative morbidity. For neuromuscular blockade reversal sugammadex can be used which has a very good efficacy and favourable safety profile; the greatest benefit from its use has been shown in patients aged > 65 years, with ASA score ≥ III or body mass index > 35, and in patients undergoing laparoscopic surgery. The administration of sugammadex prevents the development of postoperative complications and increases safety of the patients. Currently, sugammadex can be considered as a standard of care and should be offered to a much wider range of patients than has been the case to date.
Due to the increase in fungal resistance to existing drugs, a need exists to search for new antifungals. This study aimed to evaluate the antifungal activity of α, β, and δ-damascone and inclusion complexes with β-cyclodextrin against different Candida spp. The inclusion complex of β-damascone was prepared by the co-evaporation method using three molar proportions (1:1; 2:1; 3:1 (βDA-βCD)) and analyzed using Fourier transform infrared spectroscopy (FTIR). Standard Candida albicans (CA INCQS 40,006), Candida krusei (CK INCQS 40,095), and Candida tropicalis (CT INCQS 40,042) strains were used to evaluate antifungal activity. The substances were tested individually or in association with fluconazole (FCZ). The IC50 and cell viability curve constructions were performed using the microdilution method. The minimum fungicidal concentration (MFC) was determined by the subculture method in a solid medium. The α, β, and δ-DA isolated or in combination with fluconazole (FCZ) showed significant antifungal activity. β-damascone showed effective complexation in the three molar proportions assayed; however, none of the inclusion complexes was demonstrated clinically significant effects against the fungal tested. Then, all compounds have shown promising antifungal activities; however, in vivo assays are necessary to have therapeutical application in the future.
In this study, a sensitive platform was designed for the electrocatalytical oxidation and recognition of ascorbic acid (AA) based on poly(β-cyclodextrin) modified glassy carbon electrode (p(β-CD-GCE). Electropolymerization of β-CD on the surface of GCE was performed on the potential range of -1 to 1.5 V. So, a novel biopolymer was prepared on the surface of GCE towards sensitive recognition of AA in human plasma samples. The developed platform has good sensitivity and accuracy for electrooxidation and detection of AA with lower limit of quantification (LLOQ) of 1 nM and linear range of 1 nM to 100 mM. Moreover, the designed electrochemical sensor was employed for the analysis of AA on human plasma samples with high sensitivity. Based on advantages of p(β-CD) prepared by electropolymerization procedure (green, fast, homogeny, and efficient eletrocatalytical behaviour), this conductive biopolymer showed excellent analytical behaviour towards electrooxidation of AA. It is expected that the prepared polymeric interface is able to use in the analysis of biological species in clinical samples.
- MeSH
- beta-cyklodextriny MeSH
- biokompatibilní materiály MeSH
- biopolymery MeSH
- elektrochemické techniky * metody MeSH
- kyselina askorbová * MeSH
- lidé MeSH
- propylenglykoly MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Study provides an in-depth analysis of the structure-function relationship of polysaccharide anticancer drug carriers and points out benefits and potential drawbacks of differences in polysaccharide glycosidic bonding, branching and drug binding mode of the carriers. Cellulose, dextrin, dextran and hyaluronic acid have been regioselectively oxidized to respective dicarboxylated derivatives, allowing them to directly conjugate cisplatin, while preserving their major structural features intact. The structure of source polysaccharide has crucial impact on conjugation effectiveness, carrier capacity, drug release rates, in vitro cytotoxicity and cellular uptake. For example, while branched structure of dextrin-based carrier partially counter the undesirable initial burst release, it also attenuates the cellular uptake and the cytotoxicity of carried drug. Linear polysaccharides containing β-(1→4) glycosidic bonds and oxidized at C2 and C3 (cellulose and hyaluronate) have the best overall combination of structural features for improved drug delivery applications including potentiation of the cisplatin efficacy towards malignances.
- MeSH
- antitumorózní látky aplikace a dávkování MeSH
- buňky NIH 3T3 MeSH
- celulosa chemie MeSH
- cisplatina aplikace a dávkování MeSH
- dextrany chemie MeSH
- dextriny chemie MeSH
- glykosidy chemie MeSH
- inhibiční koncentrace 50 MeSH
- kyselina hyaluronová chemie MeSH
- kyslík chemie MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- myši MeSH
- nosiče léků * MeSH
- oxidace-redukce MeSH
- platina chemie MeSH
- polysacharidy chemie MeSH
- systémy cílené aplikace léků * MeSH
- techniky in vitro MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cyclin-dependent kinases (CDKs) play an important role in the cell-division cycle. Synthetic inhibitors of CDKs are based on 2,6,9-trisubstituted purines and are developed as potential anticancer drugs; however, they have low solubility in water. In this study, we proved that the pharmaco-chemical properties of purine-based inhibitors can be improved by appropriate substitution with the adamantane moiety. We prepared ten new purine derivatives with adamantane skeletons that were linked at position 6 using phenylene spacers of variable geometry and polarity. We demonstrated that the adamantane skeleton does not compromise the biological activity, and some of the new purines displayed even higher inhibition activity towards CDK2/cyclin E than the parental compounds. These findings were supported by a docking study, which showed an adamantane scaffold inside the binding pocket participating in the complex stabilisation with non-polar interactions. In addition, we demonstrated that β-cyclodextrin (CD) increases the drug's solubility in water, although this is at the cost of reducing the biochemical and cellular effect. Most likely, the drug concentration, which is necessary for target engagement, was decreased by competitive drug binding within the complex with β-CD.
- MeSH
- adamantan chemie MeSH
- antitumorózní látky chemie farmakologie MeSH
- beta-cyklodextriny chemie MeSH
- buňky K562 MeSH
- cyklin-dependentní kinasa 2 antagonisté a inhibitory MeSH
- inhibitory proteinkinas farmakologie MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- puriny chemie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Boron cluster compounds are extensively studied due to their possible use in medicinal chemistry, mainly in the boron neutron capture anticancer therapy and as new innovative pharmacophores. Concerning this research, the chiral separations of exceptionally stable anionic 7,8-dicarba-nido-undecaborate(1-) and metal bis(dicarbollide(1-) derivatives with asymmetric substitutions remain the unsolved challenge of the chiral chromatography nowadays. Although the successful enantioseparation of some anionic 7,8-dicarba-nido-undecaborate(1-) ion derivatives were achieved in CZE with native β-cyclodextrins, it has not been observed with HPLC, yet. This study aimed to systematically investigate the enantioseparation of selected compounds in HPLC using native β-cyclodextrin and brominated β-cyclodextrin. The findings revealed positively charged strong adsorption sites on a stationary phase, identified as the cationic metal impurities in the silica-gel backbone. All the anionic species under the study were at least partially enantioseparated when a chelating agent blocked these cationic sites. Consequently, the first-ever HPLC enantioseparations of the 7,8-dicarba-nido-undecaborates(1-) were achieved. The brominated β-cyclodextrin seemed to be a better chiral selector for separation of these species, whereas the native β-cyclodextrin separated the anionic cobalt bis(dicarbollide(1-). The results of this study bring new information concerning the chiral separation of anionic boron clusters and might be used in the chiral method development process on other chiral selectors. Furthermore, the possibility of chiral separation of these species could influence the ongoing research areas of anionic boron clusters.
The biological electron transfer reactions play an important role in the bioactivity of drugs; thus, the knowledge of their electrochemical behavior is crucial. The formation of radicals during oxidation or reduction, the presence of short-living intermediates, the determination of reaction mechanisms involving electron and proton transfers, all contribute to the comprehension of drug activities and the determination of their mode of action and their metabolites. In addition, if a drug is encapsulated in the cyclodextrin cavity, its electrochemical properties can change compared to a free drug molecule. Here we describe the combination of cyclic voltammetry, UV-Vis spectroelectrochemistry, GC-MS, HPLC-DAD, and HPLC-MS/MS as techniques for evaluating the oxidation mechanism of a drug encapsulated in the cavity of a cyclodextrin. The cavity of cyclodextrin plays a significant role in increasing the stability of the encapsulated products; therefore the identification of oxidation intermediates as semiquinone and benzofuranone derivatives of quercetin is possible in these conditions. The differences in oxidation potentials of the bioactive flavonol quercetin and its cyclodextrin complex relating to its antioxidant activity and the oxidation mechanism are herein discussed.
Cíl studie: Cílem studie bylo testování hypotézy, že použití sugammadexu zkracuje dobu do extubace ve srovnání s použitím neostigminu u pacientů podstupujících roboticky asistované urologické výkony. Typ studie: Monocentrická prospektivní randomizovaná studie. Typ pracoviště: Krajská a univerzitní nemocnice. Materiál a metoda: Šedesát dospělých pacientů podstupujících laparoskopický roboticky asistovaný urologický výkon bez kontraindikací k podání rokuronia, neostigminu a sugammadexu, kterým byla peroperačně monitorována hloubka nervosvalové blokády. Pacienti byli randomizováni do skupiny s antagonizací nervosvalové blokády neostigminem nebo sugammadexem. Primárním cílem byla doba od podání antidota do extubace. Výsledky: Do studie bylo zařazeno 61 pacientů ASA I–III. Doba do extubace byla významně kratší ve skupině s podáním sugammadexu v porovnání s neostigminem: 10; 3,5–35 minut, resp. 45; 16–88 minut, p < 0,00001 (data ve formátu průměr; rozmezí minimum–maximum). Pacienti ve skupině se sugammadexem byli též významně dříve transportováni z operačního sálu. V kvalitě i rychlosti zotavení po 72 hodinách nebyly mezi skupinami odlišnosti. Závěr: Sugammadex statisticky významně urychlil čas od podání do extubace u pacientů ASA I–III po roboticky asistovaném urologickém laparoskopickém výkonu v porovnání s neostigminem. Sugammadex vedl ke zkrácení času transportu pacientů z operačního sálu.
Objective: The aim of the study was to test the hypothesis that the use of sugammadex shortens the time to extubation compared to the use of neostigmine in patients undergoing robotically assisted urological procedures. Design: Monocentric prospective randomized study. Setting: Tertiary Care Hospital. Material and methods: Sixty adult patients undergoing robotic-assisted urological laparoscopic surgery without contraindications to the administration of rocuronium, neostigmine and sugammadex, with perioperative monitoring of the depth of neuromuscular blockade. Patients were randomized to the group with antagonization of the neuromuscular blockade with either neostigmine or sugammadex. Primary outcome was time to extubation from injection of the antagonist. Results: Sixty-one patients with ASA I–III were enrolled. The time to extubation was significantly shorter in the sugammadex group compared to neostigmine group: 10; 3.5–35 minutes, 45; 16–88 minutes respectively, p < 0.00001 (data shown as an average; minimum – maximum range). In addition, patients in the sugammadex group were transported significantly faster from the operating room. There were no differences in the quality and rate of recovery in 72 hours postoperatively. Conclusion: Sugammadex statistically significantly accelerated the time from administration to extubation in ASA I–III patients after robotic-assisted urologic laparoscopic surgery compared to neostigmine. Thus, sugammadex significantly accelerated the patients’ operating room turn-over time.
