Jessenius
293 stran : ilustrace, tabulky ; 24 cm
Kniha nabízí rychlou orientaci v nových látkách užívaných v onkologické léčbě.Větší část těchto látek je běžně řazena pod pojem biologická, resp. cílená léčba, kniha je však komplexnější a obsahuje také nová chemoterapeutika, resp. nová radiofarmaka. Text je doplněn schématy umožňujícími snadné pochopení mechanismu účinku.
- MeSH
- Abiraterone Acetate MeSH
- Afatinib MeSH
- Imatinib Mesylate MeSH
- Neoplasms drug therapy MeSH
- Antineoplastic Agents MeSH
- Sunitinib MeSH
- Publication type
- Monograph MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- onkologie
Cucurbit[n]urils are macrocyclic compounds capable of forming host-guest complexes with different molecules. In this study, we focused on cucurbit[7]uril (CB[7]) safety and pharmacokinetics. We investigated CB[7] cytotocixity in human renal cells ACHN using the xCELLigence system. We also determined maximum tolerated doses (MTD) and no observed adverse effect levels (NOAEL) after intramuscular (i.m.), intraperitoneal (i.p.), and intragastric (i.g.) administration in mice using clinical observation, blood biochemistry, and histopathology. At NOAELs, we studied its pharmacokinetics in plasma and kidneys. Finally, we performed a 7 day repeated-dose toxicity study at 50% of NOAEL after i.p. administration, assaying CB[7] concentration in plasma, brain, kidney, and liver; we also assessed the liver and kidney histopathology. In vitro, CB[7] did not show toxicity up to 0.94 mg/mL. MTDs in vivo were set at 300, 350, and 600 mg/kg, and NOAEL were established at 150, 100, and 300 mg/kg after i.m., i.p., and i.g. administration, respectively. Parenteral administration produced tissue damage mainly to the kidney, while i.g. administration caused only minor liver damage. Parenteral CB[7] administration led to fast elimination from blood, accompanied with kidney accumulation; absorption from the gastrointestinal tract was minimal. Short repeated i.p. administration was well tolerated. After initial CB[7] accumulation in blood and kidney, the concentrations stabilised and decreased during the experiment. Approximately 3.6% of animals showed signs of nephrotoxicity. Although CB[7] appears to be a promising molecule, nephrotoxicity may be the most critical drawback of its parenteral use, because the kidney represents the main organ of its elimination.
- MeSH
- Heterocyclic Compounds, 2-Ring * toxicity MeSH
- Imidazolidines * toxicity MeSH
- Macrocyclic Compounds * toxicity MeSH
- Maximum Tolerated Dose MeSH
- Mice MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Oxime-based molecules are used for the treatment of patients to reactivate acetylcholinesterase (AChE) function after organophosphate intoxication. However, their efficacy is limited by low penetration through the blood-brain barrier and fast elimination. In this work, the cucurbit[7]uril (CB[7]) carrier was used for the encapsulation of the clinical agent asoxime to enhance brain bioavailability and the treatment window. We present a pharmacokinetic study of asoxime and the asoxime-CB[7] complex in an in vivo mouse model. Ultrahigh-performance liquid chromatography with electrospray ionization-mass spectrometry detection was developed to determine asoxime and CB[7] in biological fluids and tissues after thorough optimization of chromatographic conditions. The dihydroxypropane-silica stationary phase using hydrophilic interaction liquid chromatography conditions provided the best chromatographic performance. The final method was validated and applied for the pharmacokinetic study of mouse plasma, urine, bile, liver, kidney, and brain samples at different times after administration of asoxime and the asoxime-CB[7] complex. The results showed a greater than 3-fold increase in the area under the curve (AUC) in the brain for asoxime administered as a complex with CB[7] relative to that for the administration of asoxime alone. The effectiveness of the treatment strategy was evaluated using a reactivation study and a functional observatory battery. Protection of brain AChE activity is crucial for saving human lives or reducing the consequences of poisoning. The asoxime administered as a complex increased the brain activity by approximately 30% compared to that with atropine alone. CB[7] coadministration improved the AChE activity by 11%, which agrees with the higher asoxime AUC assessed in the pharmacokinetic study.
- MeSH
- Acetylcholinesterase metabolism MeSH
- Cholinesterase Inhibitors administration & dosage toxicity MeSH
- Enzyme Assays MeSH
- Blood-Brain Barrier metabolism MeSH
- Mass Spectrometry MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- Imidazoles chemistry MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Drug Carriers chemistry MeSH
- Organophosphate Poisoning drug therapy MeSH
- Oximes administration & dosage pharmacokinetics MeSH
- Area Under Curve MeSH
- Bridged-Ring Compounds chemistry MeSH
- Pyridinium Compounds administration & dosage pharmacokinetics MeSH
- Cholinesterase Reactivators administration & dosage pharmacokinetics MeSH
- Sarin administration & dosage toxicity MeSH
- Chromatography, High Pressure Liquid MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Aggregation of phthalocyanines (Pcs) represents a problematic feature that decreases the potential of these macrocycles in a number of applications. In this work, we present a supramolecular approach based on the interaction of aminoadamantyl-substituted Pcs with bulky and hydrophilic cucurbit[7]uril (CB[7]) to increase the levels of Pc monomers in water. A series of zinc(II) Pcs substituted at positions α or β by an aminoadamantyl substituent (with a different level of alkylation of nitrogen) were prepared from the corresponding phthalonitriles. A 1H nuclear magnetic resonance study of the interaction of phthalonitriles with CB[7] in water confirmed the formation of an inclusion complex with an aminoadamantyl moiety with Ka values of ∼1012 M-1. The interaction of CB[7] with Pcs in water substantially weakened H-type aggregation and improved both fluorescence and singlet oxygen production, confirming that this approach is efficient for the monomerization of Pcs. In vitro evaluation of the photodynamic activity of prepared Pcs led to EC50 values in the submicromolar range on HeLa and SK-MEL-28 cells. However, the activity decreased for at least an order of magnitude after host-guest interaction with CB[7] despite better photophysical properties. This was attributed to a much lower uptake by cells due to the very bulky and hydrophilic character of the Pc-CB[7] assembly.
- Publication type
- Journal Article MeSH
Cílem našeho prezentovaného článku bylo ověření vlivu sportovní gymnastiky na rozvoj obratnostních schopností u gymnastek mladšího školního věku při přechodu do systému výkonnostních skupin. Testovanou skupinu pro tuto práci tvořila děvčata ve věku mladšího školního věku tedy 6-7 let, které přešly z přípravky do výkonnostního oddílu. Dívky závodí v Českých Budějovicích v klubu Merkur ČB. V této práci byla použita metoda kvaziexperimentu. Na začátku tréninkového období jsme udělali vstupní testování a po 3 měsících před Vánoci jsme realizovali závěrečné testování. Ověření obratnostních schopností jsme prováděli na základě standardizovaných testů. Vybrány byly čtyři testy zaměřené hlavně na obratnostní schopnosti. Zjištěné hodnoty jsme zaznamenávali do tabulek a grafů, které jsme vyhodnotili. Statistickou významnost jsme ověřili pomocí párového t-testu a věcnou významnost pomocí Cohenova d. U všech čtyř testů se potvrdila vysoká statistická významnost a spíše menší věcná významnost.
The aim of our present contribution was to verify the impact of artistic gymnastics on agility skills in younger school-aged gymnasts in the transit to competition level. The tested group was made of gymnasts aged 6-7 years that transferred into competition group. The gymnasts compete in České Budějovice in the gymnastics club Merkur CB. A quasi-experimental study was used for the thesis. In the beginning of the training period a pre-test test was made and after three months a post-test was made. The verifying of agility skills was proven through standardized tests. Four tests focused on agility skills were chosen. The measured data were put into tables and diagrams which were analysed. We verified statistical significance using a paired t-test and factual significance using Cohen d. All four tests confirmed high statistical significance and rather less substantive significance.
- MeSH
- Double-Blind Method MeSH
- Research Support as Topic MeSH
- Clorazepate Dipotassium administration & dosage MeSH
- Humans MeSH
- Paroxetine administration & dosage MeSH
- Selective Serotonin Reuptake Inhibitors administration & dosage pharmacology MeSH
- Trazodone administration & dosage MeSH
- General Adaptation Syndrome etiology drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- Comparative Study MeSH
Cíl práce: Provést fylogenetickou a molekulární analýzu virů chřipky A/H1N1pdm izolovaných v epidemické sezoně 2012/2013 od pacientů hospitalizovaných s příznaky ILI (influenza-like illnes). Materiál a metodiky: Analyzovaný soubor představoval 34 kmenů viru pandemické chřipky A/H1N1pdm v epidemické sezoně 2012/2013 v ČR. Kmeny byly podrobeny parciálnímu nebo celogenomovému sekvenování. Jednotlivé genomové segmenty se porovnaly na nukleotidové i aminokyselinové úrovni, určila se absolutní i procentní sekvenční identita a identifikovaly se fylogenetické vztahy. V posledním bodu se analyzovaly rozdíly v molekule H1 oproti aktuálnímu vakcinačnímu kmenu a identifikovala se genotypová struktura a přítomnost molekulárních markerů majících vztah k patogenitě a rezistenci na antivirotika. Výsledky: Fylogenetická analýza molekuly H1 naznačila příslušnost všech 34 A/H1N1pdm izolátů reprezentujících sezonu 2012/2013 v ČR do H1 skupiny 6 s členěním do dvou H1 sublinií 6A a 6B. Mapování rozdílů do známých antigenních oblastí molekuly H1 ukázalo dvě stabilní změny oproti aktuálnímu vakcinačnímu kmenu, a to v antigenních oblastech Sb a Ca1. Dále byly identifikovány sporadické mutace spadající do antigenní oblasti Ca2, Cb a Sb. Genotypizace odhalila ko-cirkulaci dvou příbuzných, ale jasně rozlišitelných genotypů A/H1N1pdm. Všechny izoláty se vyznačovaly citlivostí na oseltamivir. U jednoho kmene byly identifikovány dvě N1 subpopulace oseltamivir senzitivní a rezistentní v přibližně ekvimolárním poměru. Závěr: Všechny A/H1N1pdm izoláty reprezentující epidemickou sezonu 2012/2013 v ČR představovaly fenotypově jednotnou skupinu. Na nukleotidové úrovni byla divergence relativně výraznější s možností identifikace H1 sublinií i diskrétních genotypů. Molekuly H1 se vyznačovaly vysokou identitou s vakcinačním kmenem A/California/7/2009 (H1N1), což dokazovalo dostatečnou protektivitu aktuální vakcíny. Všechny kmeny se vyznačovaly citlivostí na oseltamivir, nicméně v některých případech docházelo k selekci oseltamivir-rezistentních N1 subpopulací.
Aim: To perform phylogenetic and molecular analysis of A/H1N1pdm influenza viruses isolated in the epidemic season 2012/2013 from hospitalised patients with symptoms of influenza-like illness (ILI). Material and methods: The study set included 34 strains of the A/H1N1pdm influenza virus isolated in the Czech Republic in the epidemic season 2012/2013. The strains were analysed by partial or whole-genome sequencing. The genome segments were compared at the nucleotide and amino acid levels, absolute and percentage sequence identity were determined, and phylogenetic relations were identified. The last steps were the comparison of the H1 molecule with that of the most recent vaccine strain and identification of the genotypic structure and molecular markers linked to the pathogenicity and antiviral resistance. Results: Phylogenetic analysis of the H1 molecule suggested that all 34 A/H1N1pdm isolates from the 2012/2013 season in the Czech Republic should be assigned to H1 group 6 divided into sublineages 6A and 6B. The comparison of the known antigenic regions of the H1 molecule with those in the most recent vaccine strain revealed two stable changes in antigenic regions Sb and Ca1. Furthermore, sporadic mutations were identified in antigenic regions Ca2, Cb, and Sb. Genotyping revealed co-circulation of two related but clearly distiguishable genotypes of A/H1N1pdm. All isolates showed sensitivity to oseltamivir. One strain consisted of two N1 sub-populations, one oseltamivir sensitive and the other oseltamivir resistant, in nearly equimolar proportions. Conclusion: All A/H1N1pdm isolates from the epidemic season 2012/2013 in the Czech Republic formed a phenotypically uniform group. At the nucleotide level, the divergence was relatively more pronounced and H1 sublineages and discrete genotypes were possible to identify. H1 molecules were highly identical to those of the vaccine strain A/California/7/2009 (H1N1) which showed that the current vaccine was protective enough. All strains were sensitive to oseltamivir; however, the selection of oseltamivir resistant N1 subpopulations was observed.
- MeSH
- Antiviral Agents MeSH
- Influenza, Human * genetics complications therapy MeSH
- DNA, Viral analysis MeSH
- Adult MeSH
- Genotyping Techniques MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Molecular Biology MeSH
- Mutation MeSH
- Pandemics MeSH
- Child, Preschool MeSH
- Sequence Analysis, DNA MeSH
- Aged MeSH
- Statistics as Topic MeSH
- Drug Resistance, Viral MeSH
- Influenza A Virus, H1N1 Subtype * genetics isolation & purification MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
