Contribution of international cooperation for secondary special schools

Centrum školského managementuFaculty of EducationPedagogická fakult

Humanitarian intervention by the UN

Department of Public International LawKatedra mezinárodního právaFaculty of LawPrávnická fakult

Humanitarian intervention by the UN

Department of Public International LawKatedra mezinárodního právaFaculty of LawPrávnická fakult

Optimization of Exposure Values in Computed Tomography. Perfusion CT of the Brain

Topic: Optimization of exposure values in computed tomography MUDr. Jiří Bejček, Department of Imaging Methods, FH Pilsen Introduction: Stroke is one of the most frequent diseases in the human population, the second most frequent cause of death in economically developed countries. Early diagnosis and rapid treatment play a key role. Computed tomography can be used to diagnose stroke and select optimal therapy for the patient. However, rising CT scans increase the radiation exposure of the population. Aim: The aim of this work was to analyze the stroke protocol used in the Department of Imaging Methods in Pilsen, which is used in the diagnosis of acute cerebral ischemia. In addition, the aim was to design a modification of the protocol in order to reduce the radiation exposure, maintain the diagnostic quality of the image for evaluation and verify the feasibility in daily routine. Methods: The circulation times of the original (test) protocol were analyzed retrospectively. Based on this analysis, a shortened protocol was set according to test bolus performed in CT angiography. 134 patients were examined with this protocol. Subsequently, a reduction of the voltage to 70 kV was performed and 108 patients were examined. Further protocol adjustments were made according to the width of test bolus curve. 38..

Na+/K+-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation

Maintenance of Na+ and K+ gradients across the cell plasma membrane is an essential process for mammalian cell survival. An enzyme responsible for this process, sodium-potassium ATPase (NKA), has been currently extensively studied as a potential anticancer target, especially in lung cancer and glioblastoma. To date, many NKA inhibitors, mainly of natural origin from the family of cardiac steroids (CSs), have been reported and extensively studied. Interestingly, upon CS binding to NKA at nontoxic doses, the role of NKA as a receptor is activated and intracellular signaling is triggered, upon which cancer cell death occurs, which lies in the expression of different NKA isoforms than in healthy cells. Two major CSs, digoxin and digitoxin, originally used for the treatment of cardiac arrhythmias, are also being tested for another indication—cancer. Such drug repositioning has a big advantage in smoother approval processes. Besides this, novel CS derivatives with improved performance are being developed and evaluated in combination therapy. This article deals with the NKA structure, mechanism of action, activity modulation, and its most important inhibitors, some of which could serve not only as a powerful tool to combat cancer, but also help to decipher the so-far poorly understood NKA regulation

Repurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses

Drug repositioning is a successful approach in medicinal research. It significantly simplifies the long-term process of clinical drug evaluation, since the drug being tested has already been approved for another condition. One example of drug repositioning involves cardiac glycosides (CGs), which have, for a long time, been used in heart medicine. Moreover, it has been known for decades that CGs also have great potential in cancer treatment and, thus, many clinical trials now evaluate their anticancer potential. Interestingly, heart failure and cancer are not the only conditions for which CGs could be effectively used. In recent years, the antiviral potential of CGs has been extensively studied, and with the ongoing SARS-CoV-2 pandemic, this interest in CGs has increased even more. Therefore, here, we present CGs as potent and promising antiviral compounds, which can interfere with almost any steps of the viral life cycle, except for the viral attachment to a host cell. In this review article, we summarize the reported data on this hot topic and discuss the mechanisms of antiviral action of CGs, with reference to the particular viral life cycle phase they interfere with

VALLEX 4.5

VALLEX 4.5 provides information on the valency structure (combinatorial potential) of Czech verbs in their particular senses (almost 4 700 verbs in more than 11 080 lexical units, supplemented with more than 290 nouns in more than 350 lexical units forming complex predicates with light verbs). VALLEX 4.5 is an enhanced successor of VALLEX 3.0, 3.5, and 4.0. In addition to the information stored there, VALLEX 4.5 provides a detailed description of reflexive verbs, i.e., verbs with the reflexive "se" or "si" as an obligatory part of their verb lexemes. VALLEX 4.5 covers 1 525 reflexive verbs in 1 545 lexical units (2 501 when aspectual counterparts counted separately). In order to satisfy different needs of different potential users, the lexicon is distributed (i) online in a HTML version (the data allows for an easy and fast navigation through the lexicon) and (ii) in this distribution in a machine-tractable form, so that the VALLEX data can be used in NLP applications

PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer

Purpurin 18 derivatives with a polyethylene glycol (PEG) linker were synthesized as novel photosensitizers (PSs) with the goal of using them in photodynamic therapy (PDT) for cancer. These compounds, derived from a second-generation PS, exhibit absorption at long wavelengths; considerable singlet oxygen generation and, in contrast to purpurin 18, have higher hydrophilicity due to decreased logP. Together, these properties make them potentially ideal PSs. To verify this, we screened the developed compounds for cell uptake, intracellular localization, antitumor activity and induced cell death type. All of the tested compounds were taken up into cancer cells of various origin and localized in organelles known to be important PDT targets, specifically, mitochondria and the endoplasmic reticulum. The incorporation of a zinc ion and PEGylation significantly enhanced the photosensitizing efficacy, decreasing IC50 (half maximal inhibitory compound concentration) in HeLa cells by up to 170 times compared with the parental purpurin 18. At effective PDT concentrations, the predominant type of induced cell death was apoptosis. Overall, our results show that the PEGylated derivatives presented have significant potential as novel PSs with substantially augmented phototoxicity for application in the PDT of cervical, prostate, pancreatic and breast cancer

Steroid Glycosides Hyrcanoside and Deglucohyrcanoside: On Isolation, Structural Identification, and Anticancer Activity

Cardiac glycosides (CGs) represent a group of sundry compounds of natural origin. Most CGs are potent inhibitors of Na+/K+-ATPase, and some are routinely utilized in the treatment of various cardiac conditions. Biological activities of other lesser known CGs have not been fully explored yet. Interestingly, the anticancer potential of some CGs was revealed and thereby, some of these compounds are now being evaluated for drug repositioning. However, high systemic toxicity and low cancer cell selectivity of the clinically used CGs have severely limited their utilization in cancer treatment so far. Therefore, in this study, we have focused on two poorly described CGs: hyrcanoside and deglucohyrcanoside. We elaborated on their isolation, structural identification, and cytotoxicity evaluation in a panel of cancerous and noncancerous cell lines, and on their potential to induce cell cycle arrest in the G2/M phase. The activity of hyrcanoside and deglucohyrcanoside was compared to three other CGs: ouabain, digitoxin, and cymarin. Furthermore, by in silico modeling, interaction of these CGs with Na+/K+-ATPase was also studied. Hopefully, these compounds could serve not only as a research tool for Na+/K+-ATPase inhibition, but also as novel cancer therapeutics