Akutní alkoholová hepatitida je život ohrožující stav s nepříznivou prognózou charakterizovaný ikterem a deteriorací jaterních funkcí za podmínky prokázaného abúzu alkoholu. Před zahájením terapie je nutné vyloučit spolupodíl jiné etiologie a zhodnotit závažnost stavu dle některého ze skórovacích systémů. Zatím jedinou specifickou terapií je systémová kortikoterapie, která se podává pouze pacientům s těžkou formou akutní hepatitidy. Podpůrnou léčbu by pak měli obdržet všichni pacienti bez výjimky. V rámci studií byla zkoumána další léčiva a postupy, z nichž některé se zdají být slibné.
Acute alcoholic hepatitis is a life-threatening condition with an unfavorable prognosis, characterized by jaundice and acute deterioration of liver function in the context of proven alcohol abuse. Prior to initiating therapy, it is essential to exclude other potential etiologies and assess disease severity using validated scoring systems. To date, systemic corticosteroid therapy remains the only specific treatment recommended for severe hepatitis. Supportive care is indispensable and should be provided to all patients. Numerous other pharmacological agents and interventions are under investigation, some of which show promising potential.
- MeSH
- Hepatitis, Alcoholic * physiopathology therapy MeSH
- Adrenal Cortex Hormones pharmacology therapeutic use MeSH
- Humans MeSH
- Nutritional Support methods MeSH
- Plasmapheresis methods MeSH
- Liver Transplantation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
The potentials of electrochemical processes in ideal aqueous media are related to the potential of a normal hydrogen electrode (NHE). However, in non-ideal media, the potentials of a metallocene redox couple are used as a reference. Such measurements with free metallocene in solution are complicated by adsorption and mass transport phenomena and solvation effects. Herein, a platinum electrode with an anchored ferrocene moiety (Pt,Fc) was used for cyclic voltammetric measurements of the potential of ferrocene/ferrocenium (Fc/Fc+) redox transformation in not only non-aqueous but, for the first time, aqueous solutions as well. This enabled us to eliminate the aforementioned problems associated with the application of free metallocene molecules in solution and, thus, to relate the midpoint potential (Epm) of the Fc/Fc+ redox couple to a NHE. After elimination of the liquid junction potential in an aqueous 0.1 M KCl solution at 25 °C, the average intraday Epm value obtained with freshly prepared Pt,Fc electrodes was found to be 0.312 ± 0.008 V versus the secondary Ag|AgCl electrode. The Pt,Fc electrode can be applied for the standardization of electrochemical measurements and investigation of solvation phenomena at interfaces in non-ideal media.
- Publication type
- Journal Article MeSH
IMPORTANCE: Important advances have been made in extracorporeal blood purification therapies (EBPTs) due to new technologies and biomaterials; however, the lack of established guidelines is a factor in great variability in clinical practice. This aspect is accentuated in pediatric intensive care given the small number of patients with diverse diagnoses treated with EBPT and the technical challenges in treating small children, potentiating the risk of adverse events. OBJECTIVE: To understand what experienced users of EBPT think about its relevant issues, insight that may have implications for the design of future studies, and the application of EBPTs in patient care. EVIDENCE REVIEW: Literature search was conducted using the PubMed and Embase databases between January 1, 2020, and July 15, 2024, and a combination of key medical terms. A panel of experts was formed (composed of 15 authors and pediatric intensivists) to develop a consensus statement using a modified Delphi-based model between 2022 and 2024. The panel's core team drafted the initial questionnaire, which explored EBPT use in pediatric intensive care units (PICUs), including clinical indications for initiating and discontinuing use and outcomes for assessing effectiveness and safety. SurveyMonkey was used in the distribution, completion, and revision of the questionnaire, and findings were analyzed. Panelists were asked to rank answer choices. Numerical value for each ranking was translated to a percentage defining the strength of consensus (>90% agreement from panelists signifying strong consensus; <49% signifying no consensus). FINDINGS: A total of 116 survey responses were received from panelists from 8 European countries. Strong consensus was achieved on 6 of 24 questions and consensus (75%-90% agreement) was reached on 18 of 24 questions. According to the panelists, the continuous renal replacement therapy standard or enhanced adsorption hemofilter and plasma exchange were of interest, representing the most applied EBPTs across various applications. While evidence on hemoadsorption is growing, it remains limited. CONCLUSIONS AND RELEVANCE: This consensus statement on EBPTs in critically ill pediatric patients was developed by an international panel of experts in areas where clinical evidence is still limited. This consensus statement could support pediatric intensivists in bedside decision-making and guide future research on EBPTs in PICUs.
- MeSH
- Delphi Technique MeSH
- Child MeSH
- Hemofiltration methods standards MeSH
- Intensive Care Units, Pediatric * standards MeSH
- Consensus * MeSH
- Humans MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
Biotransformation of steroids by fungi has been raised as a successful, eco-friendly, and cost-effective biotechnological alternative for chemical derivatization. Endophytic fungi live inside vegetal tissues without causing damage to the host plant, making available unique enzymes that carry out uncommon reactions. Moreover, using nanofibrous membranes as support for immobilizing fungal cells is a powerful strategy to improve their performance by enabling the combined action of adsorption and transformation processes, along with increasing the stability of the fungal cell. In the present study, we report the use of polyacrylonitrile nanofibrous membrane (PAN NFM) produced by electrospinning as supporting material for immobilizing the endophytic fungus Penicillium citrinum H7 aiming the biotransformation of progesterone. The PAN@H7 NFM displayed a high progesterone transformation efficiency (above 90%). The investigation of the biotransformation pathway of progesterone allowed the putative structural characterization of its main fungal metabolite by GC-MS analysis. The oxidative potential of P. citrinum H7 was selective for the C-17 position of the steroidal nucleus.
- MeSH
- Biotransformation MeSH
- Nanofibers * chemistry MeSH
- Progesterone MeSH
- Publication type
- Journal Article MeSH
Léčebná výměnná plazmaferéza (therapeutic plasma Exchange – TPE) má nezastupitelné místo v léčbě některých typů trombotických mikroangiopatií a je léčbou volby u trombotické trombocytopenické purpury. TPE je podle American Society for Apheresis (ASFA) definována jako terapeutický extrakorporální postup, při kterém je plazma pacienta oddělena od ostatních krevních složek. Jedná se sice o invazivní techniku vyžadující kvalitní žilní přístup, na druhé straně je TPE vysoce bezpečná, a při správném provedení jsou komplikace raritní, lze ji v případě potřeby zahájit během desítek minut a v zásadě nemá žádné reálné kontraindikace. Oddělení plazmy od ostatních složek krve je zajištěno centrifugací nebo membránovou filtrací. Jako náhradní roztok se v různých poměrech a kombinacích používají krystaloidy, 5% roztok albuminu a čerstvě zmražená dárcovská plazma, nebo se v poslední době stále častěji používá plazma ošetřená solvent-detergentem. Během jednoho výkonu se má vyměnit nejméně celý objem plazmy pacienta (total plasma volume – TPV), čímž dojde k výměně, a tedy nahrazení necelých 70 % TPV. Léčba TTP plazmaferézou by měla být zahájena co nejdříve, již při vyslovení podezření na TTP, často ještě před znalostí výsledků aktivity enzymu ADAMTS13. Před zahájením léčby TPE je nutné pamatovat na odběr vzorků krve na vyšetření ADAMTS13 a dalších vyšetření, případně uchování vzorků plazmy, protože interpretace výsledků vzorků odebraných po provedené TPE může být chybná. Účinnost TPE je dána dvěma mechanizmy: 1) odstranění mediátoru onemocnění nebo složek plazmy přispívajících k patogeneze daného stavu; 2) dodání chybějící či nefunkční složky plazmy v případě použití plazmy jako náhradního roztoku. Efektivita TPE se u jednotlivých forem trombotických mikroangiopatií různí, od jednoznačného a promptního efektu u TTP až po nulový efekt u některých forem atypického hemolyticko-uremického syndromu.
Therapeutic plasma exchange (TPE) has an irreplaceable place in the treatment of some types of thrombotic microangiopathies. In TTP, it has become the standard of care. TPE is defined by the American Society for Apheresis (ASFA) as a therapeutic extracorporeal procedure in which the patient‘s plasma is separated from other blood components. Although it is an invasive technique requiring high-quality venous access, TPE is quite safe, and when performed correctly, complications are rare. It can be started within tens of minutes if necessary, and it has essentially no real contraindications. Separation of plasma from other blood components is ensured by centrifugation or membrane filtration. Crystalloids, 5% albumin solution and freshly frozen donor plasma are used as a replacement solution in various proportions and combinations and nowadays, solvent-detergent-treated plasma is used increasingly. At least one total plasma volume (TPV) of the patient should be replaced in one procedure, with less than 70% of the TPV being replaced. It is important to remember to collect blood samples for ADAMTS13 and other tests, or preserve plasma samples, before starting TPE treatment, as interpretation of results from samples collected after TPE may be erroneous. The efficacy of TPE is determined by two mechanisms: 1) removal of the disease mediator or plasma components contributing to the pathogenesis of the condition; 2) delivery of the missing or dysfunctional plasma component when plasma is used as a replacement solution. The efficacy of TPE varies between the various forms of thrombotic microangiopathies, ranging from a clear and prompt effect in TTP to no effect at all in some forms of atypical haemolytic uraemic syndrome.
Atypický (komplementem mediovaný) hemolyticko-uremický syndrom (aHUS) je vzácné onemocnění s vysokým rizikem závažného orgánového postižení a smrti. Řadí se mezi trombotické mikroangiopatie a je charakterizován kombinací neimunitní hemolytické anemie, konsumpční trombocytopenie a poškození endotelu s následnou poruchou mikrocirkulace vedoucí k ischemickému poškození cílových orgánů, zejména ledvin. Laboratorní a klinické charakteristiky trombotických mikroangiopatií však splňuje celá řada stavů různé etiologie, což značně ztěžuje diferenciální diagnostiku tohoto onemocnění. Příčinou aHUS je geneticky podmíněné či získané narušení rovnováhy mezi aktivátory a regulátory alternativní dráhy komplementu, vedoucí k její trvalé aktivaci, tvorbě terminálních lytických komplexů a orgánovému postižení. U více než 50 % nemocných s aHUS je možné identifikovat mutaci v genech pro komplementární faktory, asi u 5–10 % pak nacházíme protilátky proti složkám komplementu (resp. faktoru H). U nositelů mutací může díky inkompletní genetické penetranci klinické onemocnění propuknout až v přítomnosti spouštěčů amplifikace komplementu, jako jsou např. infekce, operace či těhotenství. Identifikace kauzální mutace není pro diagnózu aHUS nezbytná, je ale důležitá pro stanovení prognózy, rizika relapsu při přerušení léčby či po transplantaci ledviny. Prognóza tohoto onemocnění se v posledních letech dramaticky zlepšila díky možnosti specifické léčby spočívající v podávání inhibitorů C5 složky komplementu, přesto zůstává limitována zejména rychlou a správnou diagnostikou a včasným zahájením léčby. Dosud nevyřešenými otázkami jsou také délka léčby, podmínky jejího ukončení či přerušení a také další sledování pacientů po prodělané atace tohoto vzácného onemocnění.
Atypical (or complement-mediated) haemolytic uremic syndrome (aHUS) is a rare disease with a high risk of severe organ damage and death. As a representative of thrombotic microangiopathies, it is defined by microangiopathic haemolytic anaemia, thrombocytopenia and endothelial cell damage resulting in ischemic target organ injury, especially kidney failure. A variety of clinical scenarios can have the features of thrombotic microangiopathies thus impeding the differential diagnosis of the underlying condition. aHUS is caused by a genetic or acquired defect in the regulation of the alternative complement pathway resulting in its persistent activation, formation of terminal membrane attacking complexes, microvascular endothelial damage and ischemic organ injury. Roughly 50% of patients have rare germline variants in complement genes, detection of antibodies against complement factors (CFH) is much less common. In carriers of these genetic mutations, due to the incomplete genetic penetrance of aHUS, a clinically significant disease often requires a complement-amplifying trigger such as infection, surgery or pregnancy. Identification of germline variants is not necessary for the diagnosis of aHUS; however, it is important for the estimation of prognosis and risk of relapse after treatment termination or kidney transplant. Thanks to new specific treatment options represented by complement inhibitors, the prognosis of patients with aHUS has improved rapidly, however, it remains dependent on rapid and correct diagnostics and early treatment initiation. Further discussed and unsolved questions relate to treatment duration and the possibility of its termination as well as further management and follow-up of patients after the episode of aHUS.
- Keywords
- eculizumab,
- MeSH
- Atypical Hemolytic Uremic Syndrome * diagnosis physiopathology therapy MeSH
- Diagnosis, Differential MeSH
- Antibodies, Monoclonal, Humanized administration & dosage adverse effects therapeutic use MeSH
- Complement Inactivating Agents therapeutic use MeSH
- Humans MeSH
- Mutation genetics MeSH
- Plasmapheresis MeSH
- Renal Insufficiency etiology MeSH
- Thrombotic Microangiopathies classification MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Trombotická trombocytopenická purpura (TTP) je vzácné, život ohrožující onemocnění patřící do skupiny trombotických mikroangiopatií (TMA). Je charakterizováno přítomností mikroangiopatické hemolytické anemie, těžké trombocytopenie a ischemického postižení cílových orgánů. Podstatou onemocnění je závažný deficit metaloproteázy štěpící von Willebrandův faktor (vWF). Deficit enzymu způsobuje hromadění velkých multimerů vWF, na které se aktivně váží trombocyty, s následným vznikem mikrotrombů v cévním řečišti. Stěžejním vyšetřením pro diagnostiku TTP je prokázání snížené aktivity enzymu ADAMTS13 pod 10 % (0,1 IU/ml). Léčba TTP by měla být zahájena co nejdříve, již při vyslovení podezření na TTP, často ještě před znalostí výsledků aktivity enzymu ADAMTS13. Současný standard léčby akutní ataky získané TTP zahrnuje výměnnou plazmaferézu, imunosupresi a kaplacizumab. O úspěšnosti léčby rozhoduje rychlá diagnostika TTP vč. vyšetření aktivity ADAMTS13 a včasné zahájení komplexní léčby. Nedílnou součástí léčby je také dlouhodobé sledování aktivity onemocnění, vč. monitorace aktivity ADAMTS13.
Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disease belonging to the group of thrombotic microangiopathies (TMA). It is characterised by the presence of microangiopathic haemolytic anaemia, severe thrombocytopenia, and ischaemic end-organ damage. The underlying cause of the disease is a severe deficiency of von Willebrand factor (vWF) cleaving metalloprotease. The enzyme deficiency causes the accumulation of large multimers of vWF to which platelets bind actively, with subsequent formation of microthrombi in the microcirculation. The most important test for the diagnosis of TTP is reduced ADAMTS13 enzyme activity below 10% (0.1 IU/ml). Treatment of TTP should be initiated as early as possible when it is suspected, often before the ADAMTS13 activity results are known. The current standard of care for acute attacks of acquired TTP includes therapeutic plasma exchange, immunosuppression, and caplacizumab. A rapid diagnosis of TTP, including ADAMTS13 activity testing, and early initiation of comprehensive treatment are critical to treatment success. Long-term monitoring of disease activity, including monitoring of ADAMTS13 activity, is also a necessary part of the treatment
- Keywords
- kaplacizumab,
- MeSH
- Adrenal Cortex Hormones therapeutic use MeSH
- Single-Domain Antibodies therapeutic use MeSH
- Humans MeSH
- Antibodies, Monoclonal therapeutic use MeSH
- Plasmapheresis MeSH
- ADAMTS13 Protein metabolism MeSH
- Rituximab administration & dosage therapeutic use MeSH
- Purpura, Thrombotic Thrombocytopenic * diagnosis therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
BACKGROUND: A novel supported liquid extraction approach using small polymeric nanofibrous discs was demonstrated and applied to the analysis of real river water. Nanofibrous discs were tested to extract model mixture of 9 common water contaminants 4-nitrophenol, various chlorophenols, bisphenol A, permethrin, and fenoxycarb featuring a wide range of log P values (1.9-6.5). Polyacrylonitrile, polyhydroxybutyrate, and polylactic acid nanofibers were selected as adsorptive materials. One-step desorption was performed directly in HPLC vials, to avoid time-consuming evaporation and reconstitution steps. The discs were allowed to sediment to the bottom of the vial before injection into the chromatographic system. RESULTS: Various parameters affecting the extraction efficiency including 1-octanol volume, extraction time, ionic strength, and sample volume were investigated and optimized. Wetting the nanofiber discs with 1-octanol resulted in up to 20-fold increase in enrichment factor when compared to non-wetted polymer counterparts. The highest enrichment factors were observed for analytes with a log P range of 3.3-4.5. Our developed method showed good linearity in the range 20-200 μg/L for all analytes tested. Satisfactory repeatability with RSD <13 % were achieved covering all steps including disc preparation, wetting, extraction/elution, and chromatography analysis, and recoveries ranged from 58.93 to 121.43 %. SIGNIFICANCE: This work represents novel simple supported liquid extraction approach using impregnated polymer nanofiber discs. Using only 50 μL 1-octanol, we reduced the organic solvent compared to other extraction methods. There was no need for any plastic cartridge to hold the sorbent and direct in-vial desorption reduced the unnecessary, time-consuming steps and simplified the sample preparation protocol.
- Publication type
- Journal Article MeSH
The pungency of chili peppers, the most popular hot spice used worldwide, is caused by capsaicinoids (CPDs), the content of which can vary greatly due to varietal differences and growing conditions. For the first time, a novel simple method for the fast determination of CPDs in chili peppers and chili products was developed based on adsorptive transfer cyclic square-wave voltammetry (AdTCSWV), using adsorption of lipophilic CPDs on an unmodified glassy carbon electrode surface from methanolic extracts of chili pepper samples. The CSWV is based on short oxidation of adsorbed CPDs to quinoid products, and their subsequent reduction and re-oxidation to provide specific analytical signals with a linear range from 0.05 to 1.00 mg L-1. This principle was also implemented in tandem coulometric and amperometric detection of CPDs after HPLC separation. The two-step electrochemical detection provides increased selectivity for CPDs in case of CPDs co-elution with other electrochemically oxidizable components that cannot be reversibly reduced.
Tapinarof (3,5-dihydroxy-4-isopropylstilbene) is a therapeutic agent used in the treatment of psoriasis (VTAMA®). In this study, we examined the redox behaviour, (photo)stability, (photo)toxicity and (bio)transformation of tapinarof in the context of a structure-activity relationship study. Selected derivatives of the structurally related tapinarof were investigated, namely resveratrol, pterostilbene, pinosylvin and its methyl ether. Tapinarof undergoes electrochemical oxidation in a neutral aqueous medium at a potential of around +0.5 V (vs. Ag|AgCl|3M KCl). The anodic reaction of this substance is a proton-dependent irreversible and adsorption-driven process. The pKa value of tapinarof corresponds to 9.19 or 9.93, based on empirical and QM calculation approach, respectively. The oxidation potentials of tapinarof and its analogues correlate well with their HOMO (highest occupied molecular orbital) energy level. The ability to scavenge the DPPH radical decreased in the order trolox ≥ resveratrol > pterostilbene > tapinarof > pinosylvin ≫ pinosylvin methyl ether. It was also confirmed that tapinarof, being a moderate electron donor, is able to scavenge the ABTS radical and inhibit lipid peroxidation. The 4'-OH group plays a pivotal role in antioxidant action of stilbenols. During the stability studies, it was shown that tapinarof is subject to spontaneous degradation under aqueous conditions, and its degradation is accelerated at elevated temperatures and after exposure to UVA (315-399 nm) radiation. In aqueous media at pH 7.4, we observed an ∼50 % degradation of tapinarof after 48 h at laboratory temperature. The main UVA photodegradation processes include dihydroxylation and hydration. In conclusion, the phototoxic effect of tapinarof on a human keratinocytes cell line (HaCaT) was evaluated. Tapinarof exhibited a clear phototoxic effect, similar to phototoxic standard chlorpromazine. The IC50 values of the cytotoxicity and phototoxic effects of tapinarof correspond to 27.6 and 3.7 μM, respectively. The main HaCaT biotransformation products of tapinarof are sulfates and glucuronides.
- MeSH
- Antioxidants pharmacology chemistry MeSH
- HaCaT Cells MeSH
- Dermatitis, Phototoxic MeSH
- Keratinocytes * drug effects metabolism radiation effects MeSH
- Skin drug effects metabolism radiation effects pathology MeSH
- Humans MeSH
- Oxidation-Reduction * MeSH
- Resveratrol pharmacology analogs & derivatives chemistry MeSH
- Stilbenes * pharmacology chemistry MeSH
- Ultraviolet Rays MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
