Translacija učinkovitosti piridinijevih oksima kod trovanja tabunom iz in vitro sustava u in vivo primjenu

Even if organophosphorus (OP) nerve agents were banned entirely, their presence would remain a problem as weapons of terror (like in Syria). Oxime antidotes currently used in medical practice still fall short of their therapeutic purpose, as they fail to fully restore the activity of cholinesterases, the main target for OPs. As orphan drugs, these antidotes are tested too seldom for anybody’s benefit. Over the last few decades, search for improved reactivators has reached new levels, but the translation of data obtained in vitro to in vivo application is still a problem that hinders efficient therapy. In this study, we tested the strengths and weaknesses of extrapolating pyridinium oxime antidotes reactivation efficiency from in vitro to in vivo application. Our results show that this extrapolation is possible with well-determined kinetic constants, but that it also largely depends on oxime circulation time and its tissue-specific distribution. This suggests that pharmacokinetic studies should be planned at the early stages of antidote development. Special attention should also be given to improving oxime distribution throughout the organism to overcome this major constraint in improving overall OP therapy.Iako su organofosforni živčani bojni otrovi potpuno zabranjeni za upotrebu, njihova je prisutnost i dalje velik problem, posebice kao kemijsko oružje u terorističkim napadima (poput nedavnih u Siriji). Oksimi koji se danas koriste kao protuotrovi u tretmanu nemaju dostatno djelovanje na reaktivaciju aktivnosti kolinesteraza, glavnih meta djelovanja organofosfornih spojeva. Valja napomenuti kako se klinička testiranja ovih protuotrova rijetko provode zbog svoje iznimne specifičnosti. Tijekom zadnjih desetljeća učinjen je napredak u istraživanju novih učinkovitijih protuotrova, međutim još je uvijek veliki nedostatak u poboljšavanju terapije translacija in vitro dobivenih rezultata u in vivo primjenu. Ovom studijom ispitali smo mogućnosti ekstrapolacije reaktivacijske učinkovitosti određene za oksimske protuotrove iz in vitro u in vivo sustav. Naši rezultati pokazuju kako je ova translacija moguća uz detaljno određene kinetičke parametre in vitro i uz poznavanje distribucije oksima i vremena cirkulacije u organizmu. Takav rezultat ističe važnost planiranja i farmakokinetičkih istraživanja već u samom početku razvoja protuotrova. Također, poseban naglasak u istraživanju trebalo bi staviti i na poboljšanje tkivo-specifične distribucije oksima u organizmu čime bi se poboljšala cjelokupna terapijska učinkovitost

Inhibition of acetylcholinesterase in different structures of the rat brain following soman intoxication pretreated with huperzine A

Acetylcholinesterase (AChE) activities in different brain parts were determined quantitatively in rats treated with huperzine A, soman, and huperzine A followed by soman, using histochemical and biochemical methods. Following soman intoxication ( 1.2 x LD50, i.m.), AChE activity was decreased to 30-80% of control values depending on the brain structure. The most sensitive area was the frontal cortex and the most relatively resistant was ncl.ruber. Huperzine A treatment only caused a change in AChE activity varying from 70 to 100% of control values. In rats pretreated with huperzine A and intoxicated with soman, AChE activity was significantly higher than that observed after soman. In these animals, survival of rats pretreated with huperzine was observed while the mortality of unpretreated animals was near to 80%. The results suggest that huperzine A is good candidate for further study for clinical use as a prophylactic drug against nerve agent poisoning

Effectiveners of antidote therapy on experimental intoxication of tabun

Katedra farmakologie a toxikologieDepartment of Pharmacology and ToxicologyFarmaceutická fakulta v Hradci KrálovéFaculty of Pharmacy in Hradec Králov

Study of renal transport mechanisms of radiolabeled antibodies

Charles University in Prague, Faculty of Pharmacy in Hradec Kralove Department: Department of Pharmacology and Toxicology Candidate: Mgr. Jana Kanokova Supervisor: Doc. PharmDr. Frantisek Trejtnar, CSc. Title of rigorous thesis: Study of renal transport mechanisms of radiolabeled antibodies Utilization of monoclonal antibodies belongs to one of the important strategies in the treatment of oncological diseases. This treatment has a great advantage in precise focusing on the target structure with minimal damage to surrounding non-target tissue. The antibodies against the receptor for epidermal growth factor (EGFR) expressed in higher rate by variety of tumor types represent one of the important group. Nowadays oncology utilizes both unconjugated antibodies, and the ones conjugated with other effector components, e.g. cytostatic agents, radionuclides, toxins. One of the important limits for the antibodies conjugated with radionuclides appears to be their potential accumulation in kidneys with subsequent radiotoxic damage to the kidney tissue. The aim of this experimental study was to investigate the accumulation of three 131 I- labeled anti-EGFR antibodies - panitumumab, cetuximab and nimotuzumab using a kidney model in vitro, and compare it with renal uptake of the natural peptide ligand EGFR which was..

Nature field trip from a teacher's point of view

Thesis is focused on all aspects of having pupils of a younger school age participating in a nature field trip, as percieved from a teacher's point of view. The theory section concentrates on the definition of basic terms on given issues, legislation and organisation of the nature field trip. The practical part is formed of a questionnaire section and a discussion with the aim to find out whether schools in the Czech Republic organise these trips and if so, what experiences teachers come across. If not, what reasons let them to that decision. The object of the thesis is to analyse the outcome of the inquiry and to summarise the benefits and disadvantages which emerge for teachers from such nature field trip. Both part sof the thesis highlight the challenges teachers are facing in thein profession not only during the preparation stages but also throughout the course of the nature field trip. Additionally the practical section features actual examples of previously completed trips, including the reflection of participating teachers

Religion and religious symbols in commercial communications

Marketing and commercial communications. Forms of commercial communications. Legal regulations and ethics in an advertising focused on religious elements. Analysis of selected advertising campaigns with religous themes. Qualitative marketing research.Recommendation for the future work with themes of a religion and religious symbols

Study of renal transport mechanisms of radiolabeled antibodies

Charles University in Prague, Faculty of Pharmacy in Hradec Kralove Department: Department of Pharmacology and Toxicology Candidate: Mgr. Jana Kanokova Supervisor: Doc. PharmDr. Frantisek Trejtnar, CSc. Title of rigorous thesis: Study of renal transport mechanisms of radiolabeled antibodies Utilization of monoclonal antibodies belongs to one of the important strategies in the treatment of oncological diseases. This treatment has a great advantage in precise focusing on the target structure with minimal damage to surrounding non-target tissue. The antibodies against the receptor for epidermal growth factor (EGFR) expressed in higher rate by variety of tumor types represent one of the important group. Nowadays oncology utilizes both unconjugated antibodies, and the ones conjugated with other effector components, e.g. cytostatic agents, radionuclides, toxins. One of the important limits for the antibodies conjugated with radionuclides appears to be their potential accumulation in kidneys with subsequent radiotoxic damage to the kidney tissue. The aim of this experimental study was to investigate the accumulation of three 131 I- labeled anti-EGFR antibodies - panitumumab, cetuximab and nimotuzumab using a kidney model in vitro, and compare it with renal uptake of the natural peptide ligand EGFR which was..