Jagiellonian Center for Experimental Therapeutics

Kraków, Poland

Jagiellonian Center for Experimental Therapeutics

Kraków, Poland
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Armbruster T.,University of Bern | Lazic B.,University of Bern | Galuskina I.O.,University of Silesia | Galuskin E.V.,University of Silesia | And 3 more authors.
Mineralogical Magazine | Year: 2012

The crystal structure of the rare skarn mineral trabzonite, Ca 4[Si 3O 9(OH)]OH, from the type locality near Ikizdere, Turkey and from the Upper Chegem caldera, Northern Caucasus, Kabardino-Balkaria, Russia has been solved and refined using single-crystal X-ray data. This shows that the chemical formula should be modified from Ca 4(Si 3O 10)̇2H 2O, reported in the original trabzonite description, to an OH-bearing composition. The crystal structure, which contains Si 3O 10 trimers embedded in a framework of CaO 6-8 polyhedra, has orthorhombic symmetry, space group Ama2, a = 20.6, b = 9.1, c = 10.3 Å. The orthorhombic A-centred cell is easily obtained by transformation from the original monoclinic cell of P2 1/m symmetry. The revised formula means that trabzonite and foshagite are polymorphs; foshagite has wollastonite-like silicate chains and in contrast to trabzonite it does not contain silanol groups. The structure and composition of killalaite from both localities was also studied. Single-crystal X-ray structure refinement of killalaite from the Northern Caucasus confirmed it to be non-stoichiometric with a composition between Ca 6[Si 2O 6(OH)] 2(OH) 2 and Ca 7[Si 2O 7] 2(OH) 2(Z = 2). Trabzonite, killalaite and dellaite form a series of modular structures which differ mainly in the degree of condensation of the SiO 4 units. © 2012 Mineralogical Society.

Galuskin E.V.,University of Silesia | Kusz J.,University of Silesia | Armbruster T.,University of Bern | Galuskina I.O.,University of Silesia | And 3 more authors.
American Mineralogist | Year: 2013

Vorlanite (CaU6+)O4 [Fm3m, a = 5.3647(9) Å, V = 154.40(4) Å3, Z = 2] was found in larnite pyrometamorphic rocks of the Hatrurim formation at the Jabel Harmun locality, Judean Desert, Palestinian Autonomy. Vorlanite crystals from these larnite rocks are dark-gray with greenish hue in transmitted light. This color in transmitted light is in contrast to dark-red vorlanite [Fm3m, a = 5.3813(2) Å, V = 155.834(10)Å3, Z = 2] from the type locality Upper Chegem caldera, Northern Caucasus. Heating above 750 °C of dark-gray vorlanite from the Jabel Harmun, as well as dark-red vorlanite from Caucasus, led to formation of yellow trigonal uranate CaUO4. The unusual color of vorlanite from Jabel Harmun is assumed to be related to small impurities of tetravalent uranium.

Galuskin E.V.,University of Silesia | Galuskina I.O.,University of Silesia | Kusz J.,University of Silesia | Armbruster T.,University of Bern | And 3 more authors.
Mineralogical Magazine | Year: 2014

The new mineral species vapnikite, Ca3UO6, was found in larnite pyrometamorphic rocks of the Hatrurim Formation at Jabel Harmun in the Judean desert, Palestinian Autonomy, Israel. Vapnikite is an analogue of the synthetic ordered double-perovskite β-Ca3UO6 and is isostructural with the natural fluorperovskite - cryolite Na3AlF 6. Vapnikite Ca3UO6 (P21/n, Z = 2, a = 5.739(1), b = 5.951(1), c = 8.312(1) Å , β = 90.4(1)°, V = 283.9(1) Å 3) forms yellow-brown xenomorphic grains with a strong vitreous lustre. Small grains up to 20-30 μm in size are wedged between larnite, brownmillerite and ye'elimite. Vapnikite has irregular fracture, cleavage and parting were not observed. The calculated density is 5.322 g cm-3, the microhardness is VHN25 = 534 kg mm -2 (mean of seven measurements) corresponding to the hardness of ∼5 on the Mohs scale. The crystal structure of vapnikite Ca 3UO6 differs from that of its synthetic analogue β-Ca3UO6 by having a larger degree of Ca, U disorder. Vapnikite formed at the high-temperature retrograde stage of pyrometamorphism when larnite rocks were altered by fluids/melts of high alkalinity. © 2014 The Mineralogical Society.

PubMed | CSIC - Biological Research Center, Jagiellonian Center for Experimental Therapeutics, Jagiellonian University, Charles University and University of Salamanca
Type: Journal Article | Journal: PloS one | Year: 2015

Increased levels of a soluble form of endoglin (sEng) circulating in plasma have been detected in various pathological conditions related to cardiovascular system. High concentration of sEng was also proposed to contribute to the development of endothelial dysfunction, but there is no direct evidence to support this hypothesis. Therefore, in the present work we analyzed whether high sEng levels induce endothelial dysfunction in aorta by using transgenic mice with high expression of human sEng. Transgenic mice with high expression of human sEng on CBAxC57Bl/6J background (Sol-Eng+) and age-matched transgenic littermates that do not develop high levels of human soluble endoglin (control animals in this study) on chow diet were used. As expected, male and female Sol-Eng+ transgenic mice showed higher levels of plasma concentrations of human sEng as well as increased blood arterial pressure, as compared to control animals. Functional analysis either in vivo or ex vivo in isolated aorta demonstrated that the endothelium-dependent vascular function was similar in Sol-Eng+ and control mice. In addition, Western blot analysis showed no differences between Sol-Eng+ and control mice in the protein expression levels of endoglin, endothelial NO-synthase (eNOS) and pro-inflammatory ICAM-1 and VCAM-1 from aorta. Our results demonstrate that high levels of soluble endoglin alone do not induce endothelial dysfunction in Sol-Eng+ mice. However, these data do not rule out the possibility that soluble endoglin might contribute to alteration of endothelial function in combination with other risk factors related to cardiovascular disorders.

Czamara K.,Jagiellonian University | Czamara K.,Jagiellonian Center for Experimental Therapeutics | Natorska J.,Jagiellonian University | Kapusta P.,John Paul II Hospital | And 4 more authors.
Analyst | Year: 2015

Raman microimaging was applied to study the biochemical composition in the aortic valves obtained from patients with calcific aortic stenosis. This progressive disease affects an increasing number of elderly patients with hyperlipidemia and hypercholesterolemia. Lipid accumulation in the tissue is associated with pathogenesis and progression of cardiac valve calcification. This is in line with our finding that lipid deposits, predominantly composed of cholesterol and its esters, are frequently co-localized with calcium salt deposits, even at an early stage of their development. Overall changes in the biochemical composition of the tissue upon pathology progression are less obvious. Globally, although the cholesterol level rises, the relative lipid-to-protein content decreases. The results broaden the knowledge of biochemical alterations in dysfunctional human aortic valves and may be helpful in designing lipid lowering therapies. © The Royal Society of Chemistry 2015.

Tyrankiewicz U.,Polish Academy of Sciences | Skorka T.,Polish Academy of Sciences | Jablonska M.,Polish Academy of Sciences | Jablonska M.,AGH University of Science and Technology | And 3 more authors.
Journal of Magnetic Resonance Imaging | Year: 2013

Purpose: To assess the cardiac response to low (0.15-0.5 mg/kg i.p.) and high (1.5-20 mg/kg i.p.) doses of dobutamine in Tgαq*44 mice with dilated cardiomyopathy at the stage of advanced heart failure. Materials and Methods: Inotropic, lusitropic, and chronotropic response to β1-adrenergic stimulation was assessed by the cine magnetic resonance imaging (MRI) protocol based on the electrocardiogram (ECG)-triggered bright-blood images of one midventricular short-axis slice. Results: In wildtype mice increasing doses of dobutamine resulted in subsequent increase in the left ventricular function and heart rate acceleration, but significant inotropic, lusitropic, and chronotropic cardiac response was observed only after high doses of dobutamine, what is typical. In the Tgαq*44 mice low doses of dobutamine significantly increased inotropic and lusitropic cardiac performance without chronotropic changes. An increased heart rate was observed only after high doses of dobutamine, but then inotropic and lusitropic cardiac functional reserve was lost. Conclusion: We described MRI stress test protocol based on a low and high dose of dobutamine induced response that proves useful in revealing alternation in cardiac function in mice with heart failure. © 2012 Wiley Periodicals, Inc.

Tomkiewicz-Pajak L.,Jagiellonian University | Wojcik T.,Jagiellonian Center for Experimental Therapeutics | Chlopicki S.,Jagiellonian Center for Experimental Therapeutics | Chlopicki S.,Jagiellonian University | And 8 more authors.
International Journal of Cardiology | Year: 2015

Background: Thrombotic complications are common in adult patients who have had a Fontan operation early in life for treatment of congenital heart disease. Objective: To characterize platelet function and responsiveness to aspirin in relation to thrombogenesis, systemic inflammation, and markers of endothelial function in adults with Fontan circulation (FC). Methods: Thirty-four FC patients (age 18-40 years; 62% taking aspirin chronically and 38% not taking aspirin) and 32 age- and sex-matched healthy controls were studied. Platelet function was evaluated by measurement of basal concentrations of thromboxane B2 (TXB2) and sCD40L and ex-vivo generation of TXB2 and sCD40L. Plasma concentrations of thrombin-antithrombin, endothelin-1, vWF, IL-6, IL-8, MCP-1, MIP-1β, TNFα, sVCAM-1, and syndecan-1 also were measured. Results: Platelet numberswere significantly lower in FC patients than in controls, but the patients had significantly higher platelet activity, as evidenced by higher TXB2 and sCD40L concentrations and higher ex vivo generation of TXB2. Chronic aspirin treatment had no effect on plasma concentrations of TXB2 and sCD40L in FC, but in 52% of aspirin-treated FC subjects, TXB2 concentrations remained elevated at 60 min of TXB2 generation, indicating aspirin resistance. In addition, FC patients had increased levels of thrombin-antithrombin, endothelin-1, vWF, IL-8, MCP-1, MIP-1β, TNFα, sVCAM-1, and syndecan-1 but not of IL-6. Conclusion: Adults with FC had lower platelet numbers but increased platelet activity, increased thrombogenesis, systemic inflammation, and endothelial dysfunction. A significant proportion of aspirin-treated FC adults had aspirin resistance, which may be at least in part responsible for their increased incidence of thrombotic complications. © 2014 Elsevier Ireland Ltd. All rights reserved.

Nowak W.N.,Jagiellonian University | Nowak W.N.,Jagiellonian Center for Experimental Therapeutics | Borys S.,University Hospital | Kusinska K.,Jagiellonian University | And 9 more authors.
Journal of Diabetes Investigation | Year: 2014

Aims/Introduction: Type 2 diabetes is often complicated by diabetic foot syndrome (DFS). We analyzed the circulating stem cells, growth factor and anti-oxidant gene expression profiles in type 2 diabetes patients without or with different forms of DFS. Materials and Methods: Healthy volunteers (n = 13) and type 2 diabetes patients: (i) without DFS (n = 10); or with (ii) Charcot osteoneuropathy (n = 10); (iii) non-infected (n = 17); (iv) infected (n = 11); and (v) healed ulceration were examined (n = 12). Peripheral blood endothelial progenitor cells (EPC), mesenchymal stem cells (MSC), hematopoietic stem cells (HSC) and very small embryonic-like (VSEL) cells were phenotyped using flow cytometry. Plasma cytokine concentrations and gene expressions in blood cells were measured by Luminex and quantitative real-time polymerase chain reaction assays, respectively. Results: Patients with non-complicated type 2 diabetes showed reduced HMOX1 expression, accompanied by HMOX2 upregulation, and had less circulating EPC, MSC or HSC than healthy subjects. In contrast, VSEL cells were elevated in the type 2 diabetes group. However, subjects with DFS, even with healed ulceration, had fewer VSEL cells, more CD45-CD29+CD90+MSC, and upregulated HMOX1 when compared with the type 2 diabetes group. Patients with Charcot osteopathy had lowered plasma fibroblast growth factor-2. Elevated plasma tumor necrosis factor-α and decreased catalase expression was found in all diabetic patients. Conclusions: Patients with type 2 diabetes and different forms of DFS have an altered number of circulating stem cells. Type 2 diabetes might also be associated with a changed plasma growth factor and anti-oxidant gene expression profile. Altogether, these factors could contribute to the pathogenesis of different forms of DFS. © 2013 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and Wiley Publishing Asia Pty Ltd.

Florczyk U.,Jagiellonian University | Jazwa A.,Jagiellonian University | Maleszewska M.,Jagiellonian University | Mendel M.,Jagiellonian University | And 14 more authors.
Antioxidants and Redox Signaling | Year: 2014

Aims: Nuclear factor E2-related factor 2 (Nrf2), a key cytoprotective transcription factor, regulates also proangiogenic mediators, interleukin-8 and heme oxygenase-1 (HO-1). However, hitherto its role in blood vessel formation was modestly examined. Particularly, although Nrf2 was shown to affect hematopoietic stem cells, it was not tested in bone marrow-derived proangiogenic cells (PACs). Here we investigated angiogenic properties of Nrf2 in PACs, endothelial cells, and inflammation-related revascularization. Results: Treatment of endothelial cells with angiogenic cytokines increased nuclear localization of Nrf2 and induced expression of HO-1. Nrf2 activation stimulated a tube network formation, while its inhibition decreased angiogenic response of human endothelial cells, the latter effect reversed by overexpression of HO-1. Moreover, lack of Nrf2 attenuated survival, proliferation, migration, and angiogenic potential of murine PACs and affected angiogenic transcriptome in vitro. Additionally, angiogenic capacity of PAC Nrf2-/- in in vivo Matrigel assay and PAC mobilization in response to hind limb ischemia of Nrf2-/- mice were impaired. Despite that, restoration of blood flow in Nrf2-deficient ischemic muscles was better and accompanied by increased oxidative stress and inflammatory response. Accordingly, the anti-inflammatory agent etodolac tended to diminish blood flow in the Nrf2-/- mice. Innovation: Identification of a novel role of Nrf2 in angiogenic signaling of endothelial cells and PACs. Conclusion: Nrf2 contributes to angiogenic potential of both endothelial cells and PACs; however, its deficiency increases muscle blood flow under tissue ischemia. This might suggest a proangiogenic role of inflammation in the absence of Nrf2 in vivo, concomitantly undermining the role of PACs in such conditions. © Copyright 2014, Mary Ann Liebert, Inc. 2014.

PubMed | Jagiellonian Center for Experimental Therapeutics and Jagiellonian University
Type: | Journal: European journal of pharmacology | Year: 2016

It is a well-known fact that histamine is involved in eosinophil-dependent inflammatory responses including cellular chemotaxis and migration. Nevertheless, the relative role of histamine receptors in the mechanisms of eosinophils adhesion to endothelial cells is not known. Therefore the aim of presented study was to examine the effect of selective histamine receptors ligands on eosinophils adhesion to endothelium. For that purpose the highly purified human eosinophils have been isolated from the peripheral blood. The viability and functional integrity of isolated eosinophils have been validated in several tests. Histamine as well as 4-methylhistamine (selective H4 agonist) in concentration-dependent manner significantly increased number of eosinophils that adhere to endothelium. Among the selective histamine receptors antagonist or H1 inverse agonist only JNJ7777120 (histamine H4 antagonist) and thioperamide (dual histamine H3/H4 antagonist) had direct effect on eosinophils adhesion to endothelial cells. Antagonists of H1 (diphenhydramine, mepyramine) H2 (ranitidine and famotidine) and H3 (pitolisant) histamine receptors were ineffective. To the best of our knowledge, this is the first study to demonstrate that histamine receptor H4 plays a dominant role in histamine-induced eosinophils adhesion to endothelium.

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