Alpha-Toxin in Deep Tracheal Aspirates-Preliminary Evidence for Its Presence in the Lungs of Sepsis Patients.

The pore forming alpha-toxin (hemolysin A, Hla) of () is a major virulence factor with relevance for the pathogenicity of this bacterium, which is involved in many cases of pneumonia and sepsis in humans. Until now, the presence of Hla in the body fluids of potentially infected humans could only be shown indirectly, e.g.

Monitoring Endothelin-A Receptor Expression during the Progression of Atherosclerosis.

Cardiovascular disease remains the most frequent cause of death worldwide. Atherosclerosis, an underlying cause of cardiovascular disease, is an inflammatory disorder associated with endothelial dysfunction. The endothelin system plays a crucial role in the pathogenesis of endothelial dysfunction and is involved in the development of atherosclerosis.

Fluorescent non-peptidic RGD mimetics with high selectivity for αVβ3 vs αIIbβ3 integrin receptor: novel probes for in vivo optical imaging.

Integrins are heterodimeric transmembrane protein receptors consisting of different α and β subunits. α(v)β(3) integrins are overexpressed on many tumor cells and tumor-associated angiogenic vessels, whereas α(IIb)β(3) is a receptor for, e.g.

Optimizing the bioavailability of small molecular optical imaging probes by conjugation to an albumin affinity tag.

Small molecular imaging probes are often found to be rapidly cleared from the circulation. In order to improve signal to noise ratio (SNR) by high probe accumulation in the target tissue we intended to prolong the presence of the probes in the circulation by exploiting inherent transport mechanisms. Human serum albumin (HSA) is playing an increasingly important role as a drug carrier in clinical settings and drugs directly bound to albumin or attached to albumin binding moieties have been successfully developed for treatment approaches.

Vessel size imaging (VSI) by robust magnetic resonance (MR) relaxometry: MR-VSI of solid tumors in correlation with immunohistology and intravital microscopy.

The aim of this study was to evaluate a robust magnetic resonance (MR) vessel size imaging (VSI) method for the noninvasive assessment of mean vessel size in solid tumors in a clinical dose range of ultrasmall superparamagnetic particles of iron oxide (USPIO). Therefore, USPIO-enhanced MR-VSI was performed on DU-4475, MDA-MB-435, and EOMA tumor-bearing mice xenografts with known differences in angiogenic activity and vessel morphology. MR results were compared to vessel sizes determined by immunohistochemistry (anti-CD31) and by intravital microscopy (IVM).

Design and synthesis of small-molecule fluorescent photoprobes targeted to aminopeptdase N (APN/CD13) for optical imaging of angiogenesis.

We report here the synthesis of a nonpeptide, small-molecule fluorescent imaging agent with high affinity to aminopeptidase N (APN/CD13), a key player in a variety of pathophysiological angiogenic processes. On the basis of a recently described lead structure, we synthesized three putative precursor compounds by introducing polyethylene glycol (PEG) spacers comprising amino groups for dye labeling. Different attachment sites resulted in substantial differences in target affinity, cell toxicity, and target imaging performance.

In vivo fluorescence-mediated tomography imaging demonstrates atorvastatin-mediated reduction of lesion macrophages in ApoE-/- mice.

Background: Macrophage recruitment into atherosclerotic plaques drives lesion progression, destabilization, and rupture. Chronic statin treatment reduces macrophage plaque content. Information on dynamics of macrophage recruitment would help assessing plaque vulnerability and guiding therapy.

Claudin-4-targeted optical imaging detects pancreatic cancer and its precursor lesions.

Objectives: Novel imaging methods based on specific molecular targets to detect both established neoplasms and their precursor lesions are highly desirable in cancer medicine. Previously, we identified claudin-4, an integral constituent of tight junctions, as highly expressed in various gastrointestinal tumours including pancreatic cancer. Here, we investigate the potential of targeting claudin-4 with a naturally occurring ligand to visualise pancreatic cancer and its precursor lesions in vitro and in vivo by near-infrared imaging approaches.

The inhibitory potency of local anesthetics on NMDA receptor signalling depends on their structural features.

Development of postoperative hyperalgesia depends on N-methyl-d-aspartate (NMDA) receptor activation. Local anesthetics protect against those hyperalgesic pain states and inhibit NMDA receptor activation. To outline what structural features of local anesthetics are responsible for NMDA receptor inhibition we evaluated a series of experimental lidocaine analogs (carbanilic derivates).

In vivo fluorescence-mediated tomography for quantification of urokinase receptor-dependent leukocyte trafficking in inflammation.

Background: Inflammation is characterized by leukocyte recruitment. Macrophages and neutrophils contribute to tissue damage and organ dysfunction. Modulating leukocyte invasion can protect from these adverse effects.

The novel Drosophila lysosomal enzyme receptor protein mediates lysosomal sorting in mammalian cells and binds mammalian and Drosophila GGA adaptors.

Biogenesis of lysosomes depends in mammalian cells on the specific recognition and targeting of mannose 6-phosphate-containing lysosomal enzymes by two mannose 6-phosphate receptors (MPR46, MPR300), key components of the extensively studied receptor-mediated lysosomal sorting system in complex metazoans. In contrast, the biogenesis of lysosomes is poorly investigated in the less complex metazoan Drosophila melanogaster. We identified the novel type I transmembrane protein lysosomal enzyme receptor protein (LERP) with partial homology to the mammalian MPR300 encoded by Drosophila gene CG31072.

Remifentanil directly activates human N-methyl-D-aspartate receptors expressed in Xenopus laevis oocytes.

Background: Clinical studies suggest that intraoperative administration of the clinical remifentanil formulation Ultiva (GlaxoWellcome GmbH & Co, Bad Oldesloe, Germany) increases postoperative pain and postoperative analgesic requirements, but mechanisms remain unclear. N-methyl-D-aspartate (NMDA) receptors are thought to play a major role in development of postoperative pain and opiate tolerance. The authors hypothesized that Ultiva directly stimulates human NMDA receptors.