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Pohanka, Miroslav,Karasova, Jana Zdarova,Musilek, Kamil,Kuca, Kamil,Jung, Young-Sik,Kassa, Jiri Informa Healthcare 2011 Journal of enzyme inhibition and medicinal chemist Vol.26 No.1
<P>These experiments were performed on a rat model. The rats were divided into eight groups and consequently exposed to either a saline solution (control), atropine or a combination of atropine and tabun. The reactivation efficacy of the oximes was estimated on the rats exposed to tabun, atropine and a reactivator of AChE. The oximes HI-6, obidoxime, trimedoxime, K203 and KR-22836 were used as representative compounds of commonly available and new AChE reactivators. Besides the positive effect of the administered reactivators on blood AChE activity, the sizable modulation of low molecular weight antioxidant (LMWA) levels was also determined. The LMWA levels in the the animals treated with the oxime reactivators were decreased in comparison with the animals treated by atropine alone. It was found that the levels of LMWA returned to the level found in the control animals when either trimedoxime, K203 or KR-22836 were administered. The principle of oxime reactivator function and a novel insight into AChE activity regulation and oxidative stress is discussed.</P>
Miroslav Pohanka,Oto Pavlis,Branislav Ruttkay-Nedecky,Jiri Sochor,Jakub Sobotka,Jiri Pikula,Vojtech Adam,Rene Kizek 한국미생물학회 2012 The journal of microbiology Vol.50 No.3
Francisella tularensis is the causative agent of tularemia. It is an intracellular pathogen with the ability to survive within phagosomes and induce pyroptotic cell death. In this study, we attempted to prove whether oxidative imbalance plays a significant role in tularemia pathogenesis. In our experimental model, we subcutaneously infected female BALB/c mice (dose 105 CFU of F. tularensis LVS). Liver, spleen, and blood were collected from mice at regular intervals from days 1–15 after infection. The bacterial burden was assessed by a cultivation test. The burden was unchanging from the 2nd to 6th day after infection. The bacterial burden corresponded to the plasmatic level of IFN-γ, IL-6, and liver malondialdehyde. After the phase of acute bacteraemia and the innate immunity reaction, the levels of reduced glutathione and total low molecular weight antioxidants decreased significantly and the activity of caspase-3 increased in the liver. The level of reduced glutathione decreased to 25% of the original level, and the total level of low molecular weight antioxidants was less than 50% of the initial amount. The demonstrated effects of tularemia-induced pathology had a more extensive impact on the liver than on the spleen.
Holas, Ondrej,Musilek, Kamil,Pohanka, Miroslav,Kuca, Kamil,Opletalova, Veronika,Jung, Young-Sik Korean Chemical Society 2010 Bulletin of the Korean Chemical Society Vol.31 No.6
Acetylcholinesterase reactivators are crucial antidotes for the treatment of organophosphate intoxication. Standard in vitro test was chosen using a rat brain homogenate as the source of AChE. Screening of reactivation potency was performed with two concentration of reactivator (1000 ${\mu}M$ and 10 ${\mu}M$). Results were compared to established reactivators pralidoxime, methoxime, HI-6, trimedoxime and obidoxime. More than 30 novel reactivators performed equal or better reactivation ability of POX-inhibited AChE compared to currently used reactivators. The structure-activity relationship for reactivators of paraoxon-inhibited AChE was developed.
Ondrej Holas,Kamil Musilek,Miroslav Pohanka,Kamil Kuca,Veronika Opletalova,Young-Sik Jung 대한화학회 2010 Bulletin of the Korean Chemical Society Vol.31 No.6
Acetylcholinesterase reactivators are crucial antidotes for the treatment of organophosphate intoxication. Standard in vitro test was chosen using a rat brain homogenate as the source of AChE. Screening of reactivation potency was performed with two concentration of reactivator (1000 μM and 10 μM). Results were compared to established reactivators pralidoxime, methoxime, HI-6, trimedoxime and obidoxime. More than 30 novel reactivators performed equal or better reactivation ability of POX-inhibited AChE compared to currently used reactivators. The structure-activity relationship for reactivators of paraoxon-inhibited AChE was developed.
Herwig Pieringer,Kathrin Danninger,Nikolay Tzaribachev,Nikolaus Böhler,Erich Pohanka,Manfred Herold 연세대학교의과대학 2013 Yonsei medical journal Vol.54 No.1
We systematically reviewed the literature on the infectious risk in patients treated with tumour necrosis factor blocking agents (TNF-BA) undergoing surgery: we searched the Medline (PubMed) and the online archive from the Annual European Congress of Rheumatology and the Annual Scientific Meeting of the American College of Rheumatology. Of total 1259 reports, 14 were finally analysed. With one exception all were retrospective. Four of 6 studies compared patients on TNF-BA with those not receiving TNF-BA, and found an increased risk of infection with the use of TNF-BA. None of the other studies which compared continued with discontinued treatment at surgery found an increased risk of infection, when the medication was continued perioperatively. In conclusion, while in theory there is an increased risk of infections when TNF-BA are administered perioperatively, the available literature does not necessarily support this. It rather appears that patients receiving TNF-BA are a priori at a higher risk of postoperative infections. Scheduling surgery at the end of the drug interval and adding one “safety” week prior to surgery should be an acceptable plan in daily clinical practice.
Kuca, Kamil,Cabal, Jiri,Jung, Yung Sik,Musilek, Kamil,Soukup, Ondrej,Jun, Daniel,Pohanka, Miroslav,Musilova, Lucie,Karasová,, Jana,Novotný,, Ladislav,Hrabinova, Martina Blackwell Publishing Ltd 2009 Basic & clinical pharmacology & toxicology Vol.105 No.3
<P>Abstract: </P><P>Newly developed acetylcholinesterase reactivators K117 [1,5-bis(4-hydroxyiminomethylpyridinium)-3-oxapentane dichloride] and K127 [(1-(4-hydroxyiminomethylpyridinium)-5-(4-carbamoylpyridinium)-3-oxapentane dibromide)] were tested for their potency to reactivate tabun-inhibited human brain cholinesterases. Pralidoxime and trimedoxime were chosen as standard reference reactivators. Human tissue was used, as that was closer on the real treatment of human beings. As a result, oxime K127 was found as the best tested reactivator according to the constant <I>k</I><SUB>r</SUB>, characterizing the overall reactivation process. On the contrary, the maximal reactivation ability expressed as percentage of reactivation was the best for trimedoxime. This differences were caused as a result of using the enzyme from different species. Due to this, experiments on human tissue should be conducted after <I>in vitro</I> and <I>in vivo</I> tests on animals to eliminate such important failures of promising oximes.</P>
Urinary Albumin Excretion and Vascular Function in Rheumatoid Arthritis
Herwig Pieringer,Tobias Brummaier,Bettina Piringer,Lorenz Auer-Hackenberg,Andreas Hartl,Rudolf Puchner,Erich Pohanka,Michael Schmid 대한의학회 2016 Journal of Korean medical science Vol.31 No.3
Rheumatoid arthritis (RA) is associated with significant cardiovascular (CV) morbidity and mortality. Increased urinary albumin excretion is a marker of CV risk. There are only few data on urinary albumin excretion in RA patients. Aim of the present study was to investigate urinary albumin excretion in RA patients and analyze, whether there is an association between urinary albumin excretion and vascular function as measured by the augmentation index (AIx). In a total of 341 participants (215 with RA, 126 without RA) urinary albumin-creatinine ratio (ACR) was determined and the AIx was measured. The Kolmogorov-Smirnov-test was used to cluster patient groups whose distributions of ACR can be considered to be equal. A crude analysis showed a median ACR of 6.6 mg/g in the RA group and 5.7 mg/g in patients without RA (P > 0.05). In order to account for diabetes (DM) we formed 4 distinct patient groups. Group 1: RA-/DM- (n = 74); group 2: RA+/DM- (n = 195); group 3: RA-/DM+ (n = 52); group 4: RA+/DM+ (n = 20). Clustering of these groups revealed two distinct patient groups: those without RA and DM, and those with either RA or DM or both. The latter group showed statistically significant higher ACR (median 8.1 mg/g) as the former (median 4.5 mg/g). We found no significant correlation between AIx and ACR. Urinary albumin excretion in patients with RA or DM or both is higher than in subjects without RA and DM. This can be seen as a sign of vascular alteration and increased CV risk in these patients.