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Biomedical subjects

Thomas Wenzel

Publications and source records attributed to Thomas Wenzel.

6 recordsLinked to original sources

[123I]-beta-CIT SPECT imaging shows reduced thalamus-hypothalamus serotonin transporter availability in 24 drug-free obsessive-compulsive checkers.

Numerous findings indicate alterations in brain serotonin systems in obsessive-compulsive disorder (OCD). We investigated the in vivo availability of thalamus-hypothalamus serotonin transporters (SERT) in patients with DSM-IV OCD who displayed prominent behavioral checking compulsions (OC-checkers). Four hours after injection of [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT), single photon emission computed tomography (SPECT) scans were performed in 24 medication-free non-depressed OC-checkers and 24 age- and gender-matched healthy controls. For quantification of brain serotonin transporter availability, a ratio of specific to non-displaceable [(123)I]-beta-CIT brain binding was used (V''(3)=(thalamus and hypothalamus-cerebellum)/cerebellum). Drug-free non-depressed OC-checkers showed an 18% reduced brain serotonin transporter availability in the thalamus and hypothalamus, as compared with healthy control subjects (1.38+/-0.19 vs 1.69+/-0.21; p<0.001). There was a strong negative correlation between severity of OC symptomatology (Y-BOCS scores) and SERT availability (r=-0.80; p<0.001). Moreover, we found a significant positive correlation between illness duration and serotonin transporter availability (r=0.43; p<0.05). This first report of significantly reduced [(123)I]-beta-CIT binding in the thalamus-hypothalamus region in OC-checkers suggests reduced brain serotonin transporter availability, which is more pronounced with increased severity of OC symptomatology and short duration of illness. The results provide direct evidence for an involvement of the serotonergic system in the pathophysiology of OCD.

Adult↗

Exploring the binding profiles of ConA, boronic acid and WGA by MALDI-TOF/TOF MS and magnetic particles.

Concanavalin A, boronic acid and Wheat germ agglutinin functionalized magnetic micro-particles were developed to enrich glycosylated peptides and proteins. The bead functionalities were validated according to their specificity by analyses of model proteins. Validated beads were employed for the enrichment of glycosylated human serum proteins. Eluted glycoproteins were digested by trypsin and the resulting peptides were purified by magnetic MB-HIC C8 beads. Each fraction was analyzed by MALDI-TOF MS and single peaks were subjected to MALDI-TOF/TOF MS with the objective to identify the respective proteins by database search. Search results revealed overlapping profiles of known serum glycoproteins.

Blood Proteins↗

2,5-Dihydroxyacetophenone: a matrix for highly sensitive matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis of proteins using manual and automated preparation techniques.

2,5-Dihydroxyacetophenone (DHAP) is presented as a matrix which enables highly sensitive matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometric analysis of peptides, proteins and glycoproteins on AnchorChip targets. Depending on the protein, lower fmol amounts can be detected due to the increased homogeneity and concentration of the crystallization of the analyte/matrix mixture on the anchors. Best results could be generated in the mass range of 8-100 kDa. All sample/matrix preparation steps starting from mixing of DHAP matrix solution with sample solution to the transfer of the mixture to the MALDI-TOF target can be performed manually or automatically allowing low- and high-throughput analyses.

Acetophenones↗

Adhesion, spreading, and aggregation of platelets in flowing blood and the reliability of the retention test Homburg.

Adhesion and aggregation are important parameters characterizing the function of intact platelets in flowing blood and in contact with a more or less thrombogenic surface. In the retention test Homburg (RTH), platelets are exposed to a standardized textured surface (Sysmex retention tubes) under defined conditions of flow. Platelet counts are performed before and after the Sysmex retention tube passage. The difference between these values indicates the percentage of retained platelets (retention index). Decreased retention in the RTH indicates a loss of function or defective platelet function; increase is associated with an increased activation of platelets, for example, in patients with vascular diseases. For further evaluation of the retention phenomenon the filters were fixed after cell passage and examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). SEM and TEM micrographs show activated platelets adhering and spreading on the filter surface, comparable with platelets on a disturbed endothelium. Also, we examined the influence of different G forces and centrifugation times on the retention behavior of the platelets in citrated platelet-rich plasma (PRP) and whole blood (WB). G forces influenced the retention index in PRP and WB significantly and in a different way. Finally, we used a platelet standard, as customary in the quality check, to determine the serial as well as the day-to-day precision.

Biocompatible Materials↗

Role of the retention test Homburg in evaluating platelet hyperactivity and in monitoring therapy with antiplatelet drugs.

Decreased retention in the retention test Homburg (RTH) indicates a loss of platelet function; increase is associated with an increased activation of platelets, for example, in patients with vascular diseases. Compared with other materials (e.g., collagen, glass pearls, etc.) the filter surface in the retention tubes is nonthrombogenic. Therefore, the RTH seems to be well suited for measuring an in vivo over-reactivity of platelets. In a pilot study using the RTH we evaluated the postoperative over-reactivity of platelets in 14 patients and observed a significant heterogeneity of the platelet population concerning size and stickiness. Reliable platelet function tests are also necessary for "drug monitoring," since they deliver important clinical laboratory parameters for efficient control of a therapy with antiplatelet drugs. Therefore, we evaluated in vitro how, after administration of platelet aggregation-inhibiting medications (such as acetylsalicylic acid, Prostaglandin and ReoPro in various concentrations, the adenosine diphosphate (ADP), collagen, ristocetin, or suprarenin increased retention can be reduced. The reaction of the platelets in platelet-rich plasma of different patients or donors to the addition of ADP is variable. The platelet function inhibitor effect is dose dependent. In a clinical pilot study, a significant platelet-inhibiting effect of clopidogrel using the RTH has been shown.

Abciximab↗

Selective isolation of glycoproteins and glycopeptides for MALDI-TOF MS detection supported by magnetic particles.

Glycosylation is the most common form of posttranslational modification of proteins (50-80%). The isolation, discovery, and subsequent identification of glycosylated peptides and proteins is becoming more and more important in glycoproteomics and diagnosis. MALDI-TOF mass spectrometry is an ideal technique for identifying peptides and proteins and their corresponding modifications. The enrichment of glycosylated peptides and proteins from different sources can be attained by affinity chromatography supported by functionalized magnetic particles. Covalent coating of magnetic beads with Concanavalin A (ConA) and diboronic acid was performed by carbodiimide and poly-glutaraldehyde methods, respectively. The functionalized beads were employed to establish and optimize protocols for the binding and detection of glycosylated peptides and proteins with respect to an automated workflow and the subsequent detection and identification by MALDI-TOF mass spectrometry. For several model proteins, the capture and identification could be demonstrated by SDS-PAGE and MALDI-TOF mass spectrometry. According to the type of glycosylation (high man-nose, hybrid, or complex type) the different proteins were enriched by ConA or boronic acid-functionalized beads.

Animals↗