Calibration-free concentration determination of charged colloidal nanoparticles and determination of effective charges by capillary isotachophoresis.

Although colloidal nanoparticles show an electrophoretic heterogeneity under the conditions of capillary electrophoresis, which can be either due to the particle-size distribution and/or the particle shape distribution and/or the zeta-potential distribution, they can form correct isotachophoretic zones with sharp-moving boundaries. Therefore, the technique of isotachophoresis permits to generate plugs in which the co-ions and counter ions of the original colloidal solution are removed and replaced by the buffering counter ions of the leading electrolyte. It is shown that analytical isotachophoresis can be used to measure directly, without calibration, the molar (particle) concentration of dispersed ionic colloids provided that the transference number and the mean effective charge number of the particles (within the isotachophoretic zone) can be determined with adequate accuracy. The method can also be used to measure directly the effective charge number of biomacromolecules or colloidal particles, if solutions with known molar (particle) concentration can be prepared. The validity of the approach was confirmed for a model solution containing a known molar concentration of bovine serum albumin.

Grazing incidence surface-induced dissociation: molecules sliding along a surface.

Principles of grazing incidence SID and a brief overview of previous works are summarized and the experimental setup for grazing incidence SID experiments is described. New results with fullerene C(60) are presented; these demonstrate that grazing incidence SID is not a special case of the conventional SID.

How to successfully implement E-learning for both students and teachers.

RATIONALE AND OBJECTIVES: Electronic learning (e-learning) may provide a means to enhance learning efficacy. However, introduction of e-learning often fails. We describe a strategy of how an e-learning curriculum was successfully implemented. MATERIALS AND METHODS: The curriculum was designed based on published evidence. It consists of self-directed learning, an online discussion forum, and discussion rounds. The e-content in nuclear medicine and radiotherapy was produced by the k-MED team of medical authors, web designers, and psychologists. The online courses were delivered via a dedicated learning management system. The e-content for diagnostic radiology and physics was provided as PDF/HTML script by the respective teachers who objected to participate in the k-MED project. The exam was taken online. Online evaluation of the curriculum by the students was taken at the end of the course. RESULTS: The new curriculum proved very effective. The time for the preparation for the clinical part of the radiology course could be reduced from 4 to 2 weeks. The students particularly enjoyed the self-directed learning. Although the material provided by k-MED received 90%-99% positive scores, the HTML and PDF scripts scored worse (13%-67% positive ratings). The positive results of the evaluation convinced the teachers responsible for physics and diagnostic radiology to participate in k-MED. CONCLUSIONS: As our example shows, new e-learning curricula can successfully be introduced. The strategy of implementation should be based on the existing evidence from the literature. The new curriculum helped to increase the efficacy of teaching and save time as the duration of the respective part of the course could be reduced by half.

Mercury contamination of rat amylin mimics vasoactivity and cytotoxic effects.

Rat amylin differs from human amylin (hIAPP) in that it lacks a fibril-forming capacity. As a consequence, toxic effects have been reported for human but not for rat amylin. This report demonstrates how a mercury contamination of commercial rat amylin imitates peptide-related vasoactive and cytotoxic effects on preparations of isolated blood vessels. The source of mercury contamination was believed related to the peptide synthesis. Thiol groups of cysteine-containing peptides are often protected by acetamidomethyl (Acm) which is cleaved by mercuric acetate.

Use of the incretin hormone glucagon-like peptide-1 (GLP-1) for the detection of insulinomas: initial experimental results.

The non-invasive detection of insulinomas remains a diagnostic problem that is not solved by means of somatostatin receptor scintigraphy. We investigated the biokinetics and specificity of uptake and degradation of the incretin hormone glucagon-like peptide-1 (GLP-1) in a rat insulinoma cell line (RINm5F) in order to ascertain whether radiolabelled GLP-1 may be suitable for specific visualisation of insulinomas in vivo. GLP-1 (7-36)amide was radioiodinated according to the iodogen method. The specificity of the uptake of [(125)I]GLP-1(7-36)amide by RINm5F cells was investigated. Degradation products of GLP-1 (7-36)amide in the cell medium were purified by HPLC. Their masses and amino acid sequences were determined by (252)Cf-plasma desorption mass spectrometry. Lysosomal degradation was inhibited and after differential centrifugation the amount of radiotracer incorporated into lysosomes was determined. Biodistribution studies were performed in a rat insulinoma model (NEDH rats and RINm5F cells) with [(123)I]GLP-1(7-36)amide and its more stable agonist [(123)I]exendin 3. The uptake of radiotracer into insulinoma cells reached a maximum within 5 min. It was inhibited by an excess of unlabelled peptide. [(125)I]GLP-1(7-36)amide accumulated in the cells if lysosomal degradation was inhibited. Degradation products of the peptide were found in the cell medium. We determined their mass and derived their amino acid sequence. Radiolabelling of exendin 3 was more difficult than that of GLP-1 because of the lack of tyrosine in its primary structure. Biodistribution studies showed rapid blood clearance and uptake of the radiotracer into the tumour and the pancreas. It was also possible to detect insulinomas in an animal model by external scintigraphy using radioiodinated GLP-1 (7-36)amide and exendin 3. GLP-1 (7-36)amide is specifically internalised into insulinoma cells by a receptor-mediated mechanism. Our results demonstrate that GLP-1 receptor-directed scintigraphy may be a new method for the detection of insulinomas in vivo. Due to the short half-life of GLP-1, its more stable analogue exendin 3 may better suit this purpose in vivo.

Liposomal daunorubicin (DaunoXome) in multiple myeloma: a modified VAD regimen using short-term infusion.

Liposomal daunorubicin replacing conventional anthracyclines may reduce toxicity and enhance efficacy of chemotherapy. In this phase I study, we evaluated liposomal daunorubicin (DaunoXome) in combination with vincristine and dexamethasone for toxicity, pharmacokinetics and potential efficacy in patients with multiple myeloma. The main objective was to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of liposomal daunorubicin combined with vincristine and dexamethasone (VLDD). Additionally, pharmacokinetics were determined at higher dose levels. Seventeen multiple myeloma patients were enrolled in this trial; 76% of the patients had relapsed or refractory multiple myeloma. Successive cohorts received liposomal daunorubicin at doses of 40, 60, 80 and 100 mg/m2 on day 1 in combination with vincristine 1.4 mg/m2 (day 1) and oral dexamethasone (40 mg, days 1-4). DLT occurred at 100 mg/m2. Liposomal daunorubicin at 80 mg/m2 was well tolerated in this protocol and should be used for further phase II studies with the VLDD regimen. In this phase I trial, 64% of the patients achieved a partial remission or a minor response.