Molekulare Bildgebung der Atherosklerose

Atherosklerose ist eine aktive und progressive Erkrankung, bei der vaskuläre Adhäsionsmoleküle wie VCAM-1 eine entscheidende Rolle durch Steuerung der Rekrutierung von Immunzellen in den frühen und fortgeschrittenen Plaques spielen. Ein zielgerichteter Einsatz von VCAM-1-Molekülen mit spezifischen Kontrastmitteln ist daher eine Möglichkeit, die VCAM-1-Expression zu kontrollieren, Plaquewachstum ab einem frühen Zeitpunkt zu visualisieren und eine frühe Prävention von Atherosklerose vor Beginn der Thrombusbildung zu etablieren. Des Weiteren bietet die nichtinvasive Magnetresonanz (MR)-Bildgebung den Vorteil der Kombination molekularer und morphologischer Daten. Sie ermöglicht, mithilfe von entwickelten VCAM-1-markierten Eisenoxidpartikeln, den spezifischen Nachweis entzündlicher Prozesse während der Atherosklerose. Diese Arbeit belegt, dass mit dem VCAM-1-Konzept eine vielversprechende Herangehensweise gefunden wurde und dass das, mit spezifischen superparamagnetischen Eisenoxid (USPIO) konjugierte VCAM-1-Peptid, gegenüber unspezifischer USPIOs ein erhöhtes Potenzial bei der Untersuchung der Atherosklerose in sich trägt. Im ersten Teil der Arbeit konnte im Mausmodell gezeigt werden, dass gerade das VCAM-1-Molekül ein sinnvoller Ansatzpunkt zur Darstellung und Bildgebung von Atherosklerose ist, da in der frühen Phase der Entzündung die vaskulären Zelladhäsionsmoleküle überexprimiert und auch kontinuierlich, während der fortschreitenden Plaquebildung, hochreguliert werden. Weiterhin beschreibt diese Arbeit die Funktionstüchtigkeit und das Vermögen des neu gestalteten USPIO Kontrastmittels mit dem zyklischen Peptid, in seiner Spezialisierung auf die VCAM-1 Erkennung. Experimentelle Studien mit ultra-Hochfeld-MRT ermöglichten weitere ex vivo und in vivo Nachweise der eingesetzten USPIO-VCAM-1-Partikel innerhalb der Region um die Aortenwurzel in frühen und fortgeschrittenen atherosklerotischen Plaques von 12 und 30 Wochen alten Apolipoprotein E-defizienten (ApoE-/-) Mäusen. Mit ihrer Kombination aus Histologie und Elektronenmikroskopie zeigt diese Studie zum ersten Mal die Verteilung von VCAM-1-markierten USPIO Partikeln nicht nur in luminalem Bereich der Plaques, sondern auch in tieferen Bereichen der medialen Muskelzellen. Dieser spezifische und sensitive Nachweis der frühen und fortgeschrittenen Stadien der Plaquebildung bringt auf molekularer Ebene neue Möglichkeiten zur Früherkennung von atherosklerotischen Plaques vor dem Entstehen von 8 Rupturen. Im Gegensatz zum USPIO-VCAM-1-Kontrastmittel scheiterten unspezifische USPIO Partikel an der Identifikation früher Plaqueformen und begrenzten die Visualisierung von Atherosklerose auf fortgeschrittene Stadien in ApoE-/- Mäusen.Atherosclerosis is an active and progressive condition where the vascular cell adhesion molecules as VCAM-1 play a vital role controlling the recruitment of immune cells within the early and advanced plaques. Therefore targeting of VCAM-1 molecules with specific contrast agent bears the possibility to monitor the VCAM-1 expression, visualize the plaque progression starting at the early alterations, and help to establish early prevention of atherosclerosis before the origin of the thrombus formation, of which late recognition leads to myocardial infarction. Furthermore noninvasive magnetic resonance imaging (MRI) offers the benefit of combining the molecular and anatomic data and would thus enable specific detection of VCAM-1 targeted iron oxide contrast agent within inflammatory process of atherosclerosis. This thesis exactly presents the VCAM-1 concept as a suitable molecular approach and the potential of specific ultrasmall superparamagnetic iron oxide (USPIO) conjugated to the VCAM-1 binding peptide over unspecific non-targeted USPIO particles for evaluation of atherosclerosis. This work firstly demonstrated that selection of VCAM-1 molecules offers a good and potential strategy for imaging of atherosclerosis, as these vascular cell adhesion molecules are highly expressed in the early phase of inflammation and also continuously up-regulated within the advanced plaques. Secondly, this thesis showed the proof of principle and capability of the newly designed USPIO contrast agent conjugated to the specific cyclic peptide for VCAM-1 recognition. The experimental studies including ultra-high field MRI enabled further ex vivo and in vivo detection of applied USPIO-VCAM-1 particles within the aortic root region of early and advanced atherosclerotic plaques of 12 and 30 week old apolipoprotein E deficient (ApoE-/-) mice. Using a combination of histology and electron microscopy, this study for the first time pointed to distribution of targeted USPIO-VCAM-1 particles within plaque cells expressing VCAM-1 not only in luminal regions but also in deeper medial smooth muscle cell areas. Hence functionalized USPIO particles targeting VCAM-1 molecules allow specific and sensitive detection of early and advanced plaques at the molecular level, giving the new possibilities for early recognition of atherosclerotic plaques before the appearance of advanced and prone to rupture lesions. In contrast to the functionalized USPIO-VCAM-1, utilized non-targeted USPIO particles did not succeed in early plaque 6 identification limiting visualization of atherosclerosis to advanced forms in atherosclerotic ApoE-/- mice

Dzieje pielgrzymowania z Krakowa na Jasną Górę

History of pilgrimages from Kraków to Jasna GóraDescriptions of worshippers headed from Kraków to the Shrine of Jasna Góra in the city of Częstochowa have been discovered in archives dating back to the 14th century. The early beginnings of this traditions can be linked with religious and political considerations as well as the close proximity of Częstochowa to Kraków. The tradition of pilgrimages to Jasna Góra has been maintained over the centuries despite the loss of independence by Poland as a whole. The anti-Catholic work of Poland’s post-1945 government also did not stem the flow of pilgrims from Kraków to Jasna Góra. The contemporary pilgrimage movement has its roots in the 1970s when a number of new pilgrim organizations came into existence. These included the Cistercian Foot Pilgrimage ( 1972 ), which became the 4 th part of the Kraków Foot Pilgrimage in 1998. The latter had begun in 1981. Another pilgrimage is the Dominican Foot Pilgrimage, which became an independent pilgrimage in 1992 – separate from the Archdiocesan Pilgrimage. The smallest  pilgrimage from Kraków is the Skałka Foot Pilgrimage, which has been active since 1976 and is led by the Pauline Fathers. The pastoral work and pilgrimage activity of John Paul II has also had a strong effect on each of the three pilgrimage movements from Kraków

Relations between the monks of Henryków and burghers of Münsterberg in the light of the "Book of Henryków"

The article is devoted to the relations between the monastery in Henryków and the burghers of Münsterberg (Ziębice) in the light of the Book of Henryków. On the one hand, the burghers of Ziębice were portrayed on the pages of the Book as competitors of the abbey on lands which were the object of the attention of the monastery, and also as a factor disturbing the land transactions with local knights. On the other hand, during the minority years of the sons of Prince Bolko I of Świdnica and Jawor, the city became a guarantee of law and order for the monks, which was manifested in their use of advice and help from the burghers of Münsterberg in complicated financial transactions. In the early 14th century the monks of Henryków and the burghers of Ziębice maintained very close relations, which was actually in the interest of the municipal upper class, with the cloister as a suitable place for children of the burghers, and also as a spiritual center which should be supported financially

An Overview of Anodic Oxides Derived Advanced Nanocomposites Substrate for Surface Enhance Raman Spectroscopy

Surface-enhanced Raman spectroscopy (SERS) is an analytical technique, which allows to identify traces of chemical or biological substances in many field, like pharmaceutical and food industries, homeland security, nanosensors, or environmental protection. The analytes are identified based on their vibrational spectra, unique for a given compound. The advantage of SERS is effective qualitative analysis of trace amounts of analyte, but the disadvantages are stability of substrate and repeatability of measurements. The challenge is to improve SERS substrates to minimize these drawbacks. Nowadays high-precision electron beam lithography or focused ion beam is used in SERS substrate fabrication, which is impractical for large-scale production. In recent years, researchers’ attention has focused on porous anodic oxides, with inexpensive and scalable production method, as potential materials for SERS substrates. This chapter will discuss the progress of anodic oxides used as a SERS substrate, and the brief description of conventional SERS substrate fabrication methods will be presented

The Multi-Biomarker Approach for Heart Failure in Patients with Hypertension

We assessed the predictive ability of selected biomarkers using N-terminal pro-brain natriuretic peptide (NT-proBNP) as the benchmark and tried to establish a multi-biomarker approach to heart failure (HF) in hypertensive patients. In 120 hypertensive patients with or without overt heart failure, the incremental predictive value of the following biomarkers was investigated: Collagen III N-terminal propeptide (PIIINP), cystatin C (CysC), lipocalin-2/NGAL, syndecan-4, tumor necrosis factor-α (TNF-α), interleukin 1 receptor type I (IL1R1), galectin-3, cardiotrophin-1 (CT-1), transforming growth factor β (TGF-β) and N-terminal pro-brain natriuretic peptide (NT-proBNP). The highest discriminative value for HF was observed for NT-proBNP (area under the receiver operating characteristic curve (AUC) = 0.873) and TGF-β (AUC = 0.878). On the basis of ROC curve analysis we found that CT-1 > 152 pg/mL, TGF-β 2.3 ng/mL, NT-proBNP > 332.5 pg/mL, CysC > 1 mg/L and NGAL > 39.9 ng/mL were significant predictors of overt HF. There was only a small improvement in predictive ability of the multi-biomarker panel including the four biomarkers with the best performance in the detection of HF—NT-proBNP, TGF-β, CT-1, CysC—compared to the panel with NT-proBNP, TGF-β and CT-1 only. Biomarkers with different pathophysiological backgrounds (NT-proBNP, TGF-β, CT-1, CysC) give additive prognostic value for incident HF in hypertensive patients compared to NT-proBNP alone.The study was financed by JUVENTUS PLUS grant 2012 (No. IP2011003271) of the Polish Ministry of Science and Higher Education (MNiSW) and research grant of Medical University in Lodz and MNiSW No. 502-03/5-139-02/502-54-008

Wpływ aktywności fizycznej na stężenia sklerostyny

Osteoporosis is a serious medical and socioeconomic problem of the 21st century. Mechanical load is a key regulator which controls bone formation and remodelling, with participation of osteocytes. Sclerostin is produced and released by mature osteocytes into bone surface, where it inhibits the conveyance of osteoblast proliferation and differentiation activating signals from mesenchymal cells, thus suppressing new bone formation. The goal of the study was an evaluation of the effects of a 12-week physical training programme on the levels of bone turnover markers [Sclerostin, Osteocalcin (OC), C-terminal telopeptide of type I collagen (β-CTX)] in blood serum of women with osteopenia. Materials & Methods: The study included 50 women of the Regional Menopause and Osteoporosis Centre of the WAM Teaching Hospital, at the age of 50-75 years with the diagnosis of osteopenia, obtained on the basis of hip and/or lumbar spine densitometry (T-score from -1.0 to -2.5 SD). During the initial 12 weeks (between point 1 and 2), the patients maintained their previous, normal level of physical activity. During subsequent 12 weeks (between point 2 and 3), a programme of exercise was implemented. The programme included the interval training on a bicycle ergometer, three times a week for 36 minutes. During the entire study duration, all the patients received a supplementation of calcium (500 mg) and vit. D3 (1800 IU) once daily. Serum levels of OC, alkaline phosphatase (ALP), β-CTX and sclerostin were assayed at 3 time points. Results: After the course of the exercise cycle, the OC concentration was increased, sclerostin levels decreased, while no statistical differences were observed in β-CTX levels vs. the period of physical inactivity. No correlations were found between sclerostin level changes and osteocalcin level changes during the training time, because of too small groups. Neither statistically significant were the differences in alkaline phosphatase, calcium and phosphorus levels. Conclusions: The obtained results emphasise the role of physical training as an effective stimulation method of bone formation processes in women with osteopenia. Sclerostin can be a marker of physical activity. Celem pracy była ocena wpływu 12-tygodniowego treningu ruchowego na stężenie markerów obrotu kostnego [Sklerostyny, Osteokal­cyny (OC), C-końcowego telopeptydu kolagenu typu I (β-CTX)] w surowicy krwi pacjentek z osteopenią. Materiał i metody: Do badania zostało włączonych 50 pacjentek, w wieku 50–75 lat z rozpoznaniem osteopenii. Przez pierwsze 12 tygodni (punkt 1 i 2) pacjentki prowadziły dotychczasowy poziom aktywności fizycznej. Przez kolejne 12 tygodni (między punktem 2 i 3) został włączony program ćwiczeń fizycznych. Program obejmował trening interwałowy, przeprowadzony na cykloergometrze rowerowym 3 razy w tygodniu, po 36 minut. Wszystkie pacjentki przez cały okres trwania badania pozostawały na suplementacji 500 mg wapnia i 1800 j.m. witaminy D3 dziennie. W surowicy krwi w 3 punktach czasowych oznaczano OC, fosfatazę zasadową (ALP), β-CTX oraz sklerostynę. Wyniki: Po cyklu treningu fizycznego uzyskano wzrost stężenia OC, spadek sklerostyny, natomiast nie odnotowano istotnych statystycz­nie różnic w poziomie markera β-CTX w porównaniu do okresu bez ćwiczeń. Nie wykazano korelacji pomiędzy zmianami sklerostyny a zmianami osteokalcyny w czasie treningu, prawdopodobnie ze względu na liczebność grup. Różnice w poziomach fosfatazy zasadowej, wapnia i fosforu również nie były istotne statystycznie. Wnioski: Wyniki badania podkreślają rolę treningu fizycznego, jako skutecznej metody pobudzania procesów kościotworzenia u pacjentek z osteopenią. Sklerostyna może być markerem aktywności ruchowej

Novel eco-friendly tannic acid-enriched hydrogels-preparation and characterization for biomedical application

Sodium alginate and tannic acid are natural compounds that can be mixed with each other. In this study, we propose novel eco-friendly hydrogels for biomedical applications. Thus, we conducted the following assessments including (i) observation of the structure of hydrogels by scanning electron microscope; (ii) bioerosion and the concentration of released tannic acid from subjected material; (iii) dehydrogenase activity assay to determine antibacterial activity of prepared hydrogels; and (iv) blood and cell compatibility. The results showed that hydrogels based on sodium alginate/tannic acid exert a porous structure. The immersion in simulated body fluid (SBF) results in the biomineralization process occurring on their surface while the bioerosion studies revealed that the addition of tannic acid improves hydrogels’ stability proportional to its concentration. Besides, tannic acid release concentration depends on the type of hydrogels and the highest amount was noticed for those based on sodium alginate with the content of 30% tannic acid. Antibacterial activity of hydrogels was proven for both Gram-negative and Gram-positive bacteria, the hemolysis rate was below 5% and the viability of the cells was elevated with an increasing amount of tannic acid in hydrogels. Collectively, we assume that obtained materials make the imperative to consider them for biomedical applications