- MeSH
- literatura MeSH
- významné osobnosti MeSH
- Publikační typ
- biografie MeSH
- O autorovi
- Smetana, Bedřich, 1824-1884 Autorita
- MeSH
- balneologie MeSH
- dějiny 20. století MeSH
- lázně dějiny MeSH
- lidé MeSH
- Check Tag
- dějiny 20. století MeSH
- lidé MeSH
- Publikační typ
- historické články MeSH
- Geografické názvy
- Československo MeSH
- MeSH
- kardiologie MeSH
- vnitřní lékařství MeSH
- Publikační typ
- biografie MeSH
- nekrology MeSH
- O autorovi
- Kvasnička, Jiří, 1934-2024 Autorita
Background/Objectives: Increasing drugs' stability and adequately protecting them against degradation will ensure a decrease in their price and broader availability of pharmaceutical substances. This is of great importance, especially for drugs used to treat the most common diseases in the population, such as hypertension. The study examined two newly synthesized substances from the angiotensin I-converting enzyme inhibitor (ACEI) group as potential drugs. ACEIs are among the leading drugs used in the treatment of hypertension in the world. The chemical modifications of the tested substances applied concerned the places most susceptible to degradation. The presented work analyzed the compatibility of new derivatives with selected excipients used in pharmacy. Methods: Thermogravimetric (TGA) and differential thermal analyses (c-DTA) were used as the main methods. In addition, non-thermal methods such as colorimetry analysis, Fourier-transform infrared (FTIR) and UV spectroscopy were used. Results: Based on the conducted studies, it can be concluded that the incompatibility of IND-1 with glucose anhydrous and lactose monohydrate occurs only when the mixture is stored at higher temperatures. For the remaining IND-1 and IND-2 mixtures with excipients, compatibility was demonstrated. Conclusions: The obtained results confirmed the usefulness of the applied thermal analyses (TGA and c-DTA) for assessing the compatibility of the tested potential drugs with excipients. However, in the case of incompatibility reactions of substances occurring under the influence of elevated temperatures, such as the Maillard reaction, it is necessary to use non-thermal methods to obtain the right result.
- Publikační typ
- časopisecké články MeSH
The European Society of Intensive Care Medicine (ESICM) has developed evidence-based recommendations and expert opinions about end-of-life (EoL) and palliative care for critically ill adults to optimize patient-centered care, improving outcomes of relatives, and supporting intensive care unit (ICU) staff in delivering compassionate and effective EoL and palliative care. An international multi-disciplinary panel of clinical experts, a methodologist, and representatives of patients and families examined key domains, including variability across countries, decision-making, palliative-care integration, communication, family-centered care, and conflict management. Eight evidence-based recommendations (6 of low level of evidence and 2 of high level of evidence) and 19 expert opinions were presented. EoL legislation and the importance of respecting the autonomy and preferences of patients were given close attention. Differences in EoL care depending on country income and healthcare provision were considered. Structured EoL decision-making strategies are recommended to improve outcomes of patients and relatives, as well as staff satisfaction and mental health. Early integration of palliative care and the use of standardized tools for symptom assessment are suggested for patients at high risk of dying. Communication training for ICU staff and printed communication aids for families are advocated to improve outcomes and satisfaction. Methods for enhancing family-centeredness of care include structured family conferences and culturally sensitive interventions. Conflict-management protocols and strategies to prevent burnout among healthcare professionals are also considered. The work done to develop these guidelines highlights many areas requiring further research.
- MeSH
- jednotky intenzivní péče * organizace a řízení normy MeSH
- komunikace MeSH
- lidé MeSH
- paliativní péče * normy metody MeSH
- péče o pacienty v kritickém stavu metody normy MeSH
- péče o umírající * normy metody MeSH
- rozhodování MeSH
- společnosti lékařské MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- směrnice pro lékařskou praxi MeSH
- Geografické názvy
- Evropa MeSH
Geldanamycin remains a driver in the medicinal chemistry of heat shock protein 90 (Hsp90) inhibition, even half a century after its original isolation from nature. This Perspective focuses on the properties of the benzoquinone ring of the natural product that enable a range of functionalization reactions to take place. Therefore, inherent reactivity at C-17, where the methoxy group serves as a vinylogous ester, and at C-19 that demonstrates nucleophilic, enamide-type character toward electrophiles, and also as a conjugate acceptor to react with nucleophiles, has facilitated the synthesis of semisynthetic derivatives. Thus, a range of C-17-substituted amine derivatives has been investigated in oncology applications, with a number of compounds in this series reaching clinical trials. In contrast, the 19-position of geldanamycin has received less attention, although 19-substituted derivatives offer promise with markedly reduced toxicity compared to geldanamycin itself, while retaining Hsp90 inhibitory activity albeit with diminished potency in cellular studies.
- MeSH
- benzochinony * chemie farmakologie chemická syntéza MeSH
- farmaceutická chemie metody MeSH
- lidé MeSH
- makrocyklické laktamy * chemie farmakologie chemická syntéza MeSH
- proteiny tepelného šoku HSP90 * antagonisté a inhibitory metabolismus MeSH
- protinádorové látky farmakologie chemie chemická syntéza MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
AIMS: Advanced ablation strategies are needed to treat ventricular tachycardia (VT) and premature ventricular complexes (PVC) refractory to standard unipolar radiofrequency ablation (Uni-RFA). Bipolar radiofrequency catheter ablation (Bi-RFA) has emerged as a treatment option for refractory VT and PVC. Multicentre registry data on the use of Bi-RFA in the setting of refractory VT and PVC are lacking. The aim of this Bi-RFA registry is to determine its real-world safety, feasibility, and efficacy in patients with refractory VT/PVC. METHODS AND RESULTS: Consecutive patients undergoing Bi-RFA at 16 European centres for recurring VT/PVC after at least one standard Uni-RFA were included. Second ablation catheter was used instead of a dispersive patch and was positioned at the opposite site of the ablation target. Between March 2021 and August 2024, 91 patients underwent 94 Bi-RFA procedures (74 males, age 62 ± 13, and prior Uni-RFA range 1-8). Indications were recurrence of PVC (n = 56), VT (n = 20), electrical storm (n = 13), or PVC-triggered ventricular fibrillation (n = 2). Procedural time was 160 ± 73 min, Bi-RFA time 426 ± 286 s, and mean Uni-RFA time 819 ± 697 s. Elimination of clinical VT/PVC was achieved in 67 (74%) patients and suppression of VT/PVC in a further 10 (11%) patients. In the remaining 14 patients (15%), no effect on VT/PVC was observed. Three major complications occurred: coronary artery occlusion, atrioventricular block, and arteriovenous fistula. Follow-up lasted 7 ± 8 months. Nineteen patients (61%) remained VT free. ≥80% PVC burden reduction was achieved in 45 (78%). CONCLUSION: These real-world registry data indicate that Bi-RFA appears safe, is feasible, and is effective in the majority of patients with VT/PVC.
- MeSH
- katetrizační ablace * metody MeSH
- komorová tachykardie * chirurgie patofyziologie MeSH
- komorové extrasystoly * chirurgie patofyziologie diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- recidiva * MeSH
- registrace * MeSH
- senioři MeSH
- studie proveditelnosti MeSH
- výsledek terapie 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
- Geografické názvy
- Evropa MeSH
Many enhancers control gene expression by assembling regulatory factor clusters, also referred to as condensates. This process is vital for facilitating enhancer communication and establishing cellular identity. However, how DNA sequence and transcription factor (TF) binding instruct the formation of high regulatory factor environments remains poorly understood. Here we developed a new approach leveraging enhancer-centric chromatin accessibility quantitative trait loci (caQTLs) to nominate regulatory factor clusters genome-wide. By analyzing TF-binding signatures within the context of caQTLs and comparing episomal versus endogenous enhancer activities, we discovered a class of regulators, 'context-only' TFs, that amplify the activity of cell type-specific caQTL-binding TFs, that is, 'context-initiator' TFs. Similar to super-enhancers, enhancers enriched for context-only TF-binding sites display high coactivator binding and sensitivity to bromodomain-inhibiting molecules. We further show that binding sites for context-only and context-initiator TFs underlie enhancer coordination, providing a mechanistic rationale for how a loose TF syntax confers regulatory specificity.
- MeSH
- chromatin * genetika metabolismus MeSH
- lidé MeSH
- lokus kvantitativního znaku * MeSH
- myši MeSH
- regulace genové exprese MeSH
- transkripční faktory * metabolismus genetika MeSH
- vazba proteinů MeSH
- vazebná místa genetika MeSH
- zesilovače transkripce * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
