Immune defenses are crucial for survival but costly to develop and maintain. Increased immune investment is therefore hypothesized to trade-off with other life-history traits. Here, we examined innate and adaptive immune responses to environmental heterogeneity in wild Antarctic fur seals.
View Article and Find Full Text PDFPurpose: Integrins are transmembrane receptors responsible for cell-cell adhesion and cell-extracellular matrix binding and play an important role in angiogenesis and tumour metastasis. For this reason, integrins are increasingly used as targets for molecular imaging. Up to now interest has mostly been focused on the integrin subtype αvβ3.
View Article and Find Full Text PDFUnlabelled: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Late detection of then nonresectable or metastasized tumors emphasizes the need for novel imaging approaches. Here, we report on so far nonexploited potentials of αvβ3 integrin-targeted molecular imaging technologies for detection of PDAC using genetically engineered mouse models.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
October 2013
Pattern seekers: For the two angiogenic relevant integrins α5β1 and αvβ3, functionalized derivatives of the selective antagonists 1 and 2 could target and discriminate between tumor cells in vivo based on their different integrin patterns and also delay tumor growth in vivo. In addition, the first α5β1-selective integrin antagonist that enables specific molecular imaging by positron emission tomography was developed.
View Article and Find Full Text PDFBackground: Expression of αvβ3 integrin is increased after myocardial infarction as part of the repair process. Increased expression of αvβ3 has been shown by molecular imaging with 18F-galacto-RGD in a rat model. The 68Ga-labelled RGD compounds 68Ga-NODAGA-RGD and 68Ga-TRAP(RGD)3 have high specificity and affinity, and may therefore serve as alternatives of 18F-galacto-RGD for integrin imaging.
View Article and Find Full Text PDF1,2-Diamino-propionic acid (Dap) is a very strong chelator for the [(99m)Tc(CO)(3)](+) core, yielding small and hydrophilic complexes. We prepared the lysine based Dap derivative l-Lys(Dap) in which the ε-NH(2) group was replaced by the tripod through conjugation to its α-carbon. The synthetic strategy produced an orthogonally protected bifunctional chelator (BFC).
View Article and Find Full Text PDFGallium-68 is rapidly gaining importance, as this generator-produced PET isotope is available independent of on-site cyclotrons, enabling radiopharmaceutical production with comparably simple techniques at low cost. The recently introduced TRAP chelator combines the advantage of straightforward design of multimeric ⁶⁸Ga-radiopharmaceuticals with very fast and efficient ⁶⁸Ga-labeling. We synthesized a series of five cyclo(RGDfK) peptide trimers and determined their α(v)β₃ integrin affinities in competition assays on α(v)β₃-expressing M21 human melanoma cells against ¹²⁵I-echistatin.
View Article and Find Full Text PDFBackground: Currently, 68Ga-labeled 1,4,7,10-tetraazacyclododecane-tetraacetic acid (DOTA)-peptides are the most widely used class of 68Ga radiotracers for PET, although DOTA is not optimal for 68Ga complexation. More recently, 1,4,7-triazacyclononane-triacetic acid (NOTA) and particularly triazacyclononane-phosphinate (TRAP) chelators have been shown to possess superior 68Ga binding ability. Here, we report on the efficiency, reproducibility, and achievable specific activity for fully automated 68Ga labeling of DOTA-, NOTA-, and TRAP-peptide conjugates.
View Article and Find Full Text PDFIntroduction: (18)F-Galacto-cyclo(RGDfK) is a well investigated tracer for imaging of ανβ3 expression in vivo, but suffers from the drawback of a time consuming multistep synthesis that can hardly be established under GMP conditions. In this study, we present a direct comparison of the pharmacokinetic properties of this tracer with (68)Ga-NODAGA-cyclo(RGDyK), in order to assess its potential as an alternative for (18)F-Galacto-cyclo(RGDfK).
Methods: (68)Ga labeling of NODAGA-cyclo(RGDyK) was done in full automation using HEPES-buffered eluate of an SnO(2) based (68)Ga-generator.
A symptomatic young woman with newly diagnosed systemic lupus erythematosus and secondary antiphospholipid syndrome with elevated anticardiolipin antibodies presented with small nodules on both leaflets of the mitral valve and with a consecutive high-grade mitral regurgitation, as diagnosed by echocardiography. In consideration of the preoperative and intraoperative findings, and the patient's low age, a mitral valve repair with removal of the leaflet vegetations and a ring annuloplasty were performed.
View Article and Find Full Text PDFLaboratory animal well-being can be improved by housing the animals in species-specific natural or near-to-natural environments. An enriched environment may have a similar effect on chickens. The purpose of this study was to examine if housing environment (furnished cages vs.
View Article and Find Full Text PDFPsychother Psychosom
January 2010
Background: This study aimed at the impact of medical comorbidity (MC) on response to antidepressant treatment over 6 weeks in diagnostic subtypes of patients with major depressive episode (MDE).
Methods: In a clinical sample of 241 admitted patients with MDE, MC was assessed by medical specialists and weekly response to antidepressant treatment was assessed with the Hamilton Depression Scale (HAM-D 21).
Results: Over 6 weeks of treatment, patients with melancholic depression and MC had poorer treatment response on the HAM-D scale and a worse functional outcome (GAF) as opposed to their counterparts without MC, which was first detected after 4 weeks of treatment (p = 0.
The battery cage system is being banned in the European Union before or by 2012, and the furnished cage system will be the only cage system allowed after 2012. This study was conducted to examine the different effects of caging systems, furnished cages vs. battery cages, on bird behaviors.
View Article and Find Full Text PDFTwo new ligands, 1,4,7-tris(2-mercaptoethyl)-1,4,7-triazacyclodecane (L2) and 9-methyl-1,4,7-tris(2-mercaptoethyl)-1,4,7-triazacyclodecane (L3), have been synthesized by reaction of the free triazacycloalkanes with ethylene sulfide. Complexes of L2 with Ga(III), In(III), and Fe(III), as well as Ga(III) and In(III) complexes of L3, have been characterized by single crystal X-ray diffraction. In all cases, the metal ions are coordinated in a trigonal-antiprismatic environment with varying degrees of distortion.
View Article and Find Full Text PDFBackground: There are many nucleoside metal complexes known. According to observations made, only very few of them reveal their central ion to be co-ordinated by the sugar part of their molecules. The regio- and stereosspecific exchange of the hydroxyl groups at the sugar moiety by chelating units improves its complexation ability and should give access to a new class of chiral ligands.
View Article and Find Full Text PDFUnlabelled: Multi-detector row Computed Tomography (MDCT) permits non-invasive visualization of the coronary arteries. The ability to visualize and, with limitations, to characterize non-calcified coronary atherosclerotic plaque has been described. We investigated the CT attenuation of non-calcified plaques as determined by 16-slice MDCT in comparison to intravascular ultrasound (IVUS).
View Article and Find Full Text PDFPurpose: To investigate the ability of 16-slice multidetector-row computed tomography (MDCT) to visualize coronary artery bypass graft (CABG) patency and to detect bypass stenoses.
Materials And Methods: Thirty-two patients with 94 grafts (20 mammary artery grafts, 74 venous grafts) were investigated by 16-slice MDCT using a scan protocol with 12 x 0.75 mm slice collimation (pitch 0.
Unlabelled: We compared the extent of coronary calcifications as quantified by electron beam tomography (EBT) to the predicted 10-year cardiovascular event risk based on Framingham and PROCAM algorithms in patients with a first myocardial infarction (MI).
Methods: In 156 patients (56.7 +/- 22 years), EBT was performed <4 weeks after MI.
Background: We investigated the potential of 16-slice multi-detector row spiral CT (MDCT) with retrospective ECG-gating for evaluation of coronary artery anomalies.
Methods: A total of 35 patients (23 men, 12 women, 19-81 years) in whom anomalous coronary arteries had been detected by invasive coronary angiography underwent MDCT (Sensation 16, Siemens, Germany). During one breathhold, a contrast-enhanced (90 ml, 5 ml/s) volume data set of the heart was acquired (16x0.
In 26 patients, 16-slice multidetector computed tomography (MDCT) with 0.75-mm collimation and intravascular ultrasound (IVUS) of 1 coronary artery were performed. At 100 sites within the coronary arteries, the measurement of cross-sectional luminal area and, if detectable, the cross-sectional area of atherosclerotic plaque was performed independently with IVUS and MDCT.
View Article and Find Full Text PDFObjective: To analyze the association among aortic valve calcification, cardiovascular risk factors, and coronary artery calcification using electron beam computed tomography (EBCT).
Patients And Methods: We analyzed cardiac EBCT data obtained for coronary calcium detection in 1000 consecutively enrolled patients (mean +/- SD age, 57.1 +/- 10 years; 69% men) between January 1, 1998, and July 23, 2001.
Rationale And Objectives: The exact quantification of the amount of calcification in aortic valves may be useful for the identification of risk factors for the progression of aortic valve calcification and to evaluate new therapeutic approaches for aortic valve disease. Electron beam tomography (EBT) allows the in vivo detection of calcifications in coronary vessels and in the aortic valve. The aim of this study was to validate the quantification of aortic valve calcification by EBT with in vivo and in vitro investigations.
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