Effects of opioids on human serotonin transporters.

The serotonin (5-hydroxtryptamine, 5-HT) system plays a role in analgesia and emesis. The aim of this study was to test whether opioids or ketamine inhibit the human 5-HT transporter and whether this increases free plasma 5-HT concentrations. HEK293 cells, stably transfected with the human 5-HT transporter cDNA, were incubated with morphine, hydromorphone, fentanyl, alfentanil, pethidine (meperidine), tramadol, ketamine, and the reference substance citalopram (specific 5-HT transporter inhibitor). The uptake of [(3)H]5-HT was measured by liquid scintillation counting. In a second series of experiments, study drugs were incubated with plasma of ten healthy blood donors and change of 5-HT plasma-concentrations were measured (ELISA). The end point was the inhibition of the 5-HT transporter by different analgesics either in HEK293 cells or in human platelets ex vivo. Tramadol, pethidine, and ketamine suppressed [(3)H]5-HT uptake dose-dependently with an IC50 of 1, 20.9, and 230 μM, respectively. These drugs also prevented 5-HT uptake in platelets with an increase in free plasma 5-HT. Free 5-HT concentrations in human plasma were increased by citalopram 1 μM, tramadol 20 μM, pethidine 30 μM, and ketamine 100 μM to 280 [248/312]%, 269 [188/349]%, and 149 [122/174]%, respectively, compared to controls without any co-incubation (means [95 % CI]; all p < 0.005). No change in both experimental settings was observed for the other opioids. Tramadol and pethidine inhibited the 5-HT transporter in HEK293 cells and platelets. This inhibition may contribute to serotonergic effects when these opioids are given in combination, e.g., with monoamine oxidase inhibitors or selective serotonin reuptake inhibitors.

Focal cystic high-attenuation lesions: characterization in renal phantom by using photon-counting spectral CT--improved differentiation of lesion composition

To evaluate the capability of spectral computed tomography (CT) to improve the characterization of cystic high-attenuation lesions in a renal phantom and to test the hypothesis that spectral CT will improve the differentiation of cystic renal lesions with high protein content and those that have undergone hemorrhage or malignant contrast-enhancing transformation.

Carbohydrate counting of food

Carbohydrate counting is a principal strategy in nutritional management of type 1 diabetes. The Nutri-Learn buffet (NLB) is a new computer-based tool for patient instruction in carbohydrate counting. It is based on food dummies made of plastic equipped with a microchip containing relevant food content data. The tool enables the dietician to assess the patient's food counting abilities and the patient to learn in a hands-on interactive manner to estimate food contents such as carbohydrate content.

The recoil transfer chamber - An interface to connect the physical preseparator TASCA with chemistry and counting setups

Performing experiments with transactinide elements demands highly sensitive detection methods due to the extremely low production rates (one-atom-at-a-time conditions). Preseparation with a physical recoil separator is a powerful method to significantly reduce the background in experiments with sufficiently long-lived isotopes (t1/2≥0.5 s). In the last years, the new gas-filled TransActinide Separator and Chemistry Apparatus (TASCA) was installed and successfully commissioned at GSI. Here, we report on the design and performance of a Recoil Transfer Chamber (RTC) for TASCA—an interface to connect various chemistry and counting setups with the separator. Nuclear reaction products recoiling out of the target are separated according to their magnetic rigidity within TASCA, and the wanted products are guided to the focal plane of TASCA. In the focal plane, they pass a thin Mylar window that separates the ∼1 mbar atmosphere in TASCA from the RTC kept at ∼1 bar. The ions are stopped in the RTC and transported by a continuous gas flow from the RTC to the ancillary setup. In this paper, we report on measurements of the transportation yields under various conditions and on the first chemistry experiments at TASCA—an electrochemistry experiment with osmium and an ion exchange experiment with the transactinide element rutherfordium.

Measuring substrate binding and affinity of purified membrane transport proteins using the scintillation proximity assay

The scintillation proximity assay (SPA) is a rapid radioligand binding assay. Upon binding of radioactively labeled ligands (here L-[(3)H]arginine or D-[(3)H]glucose) to acceptor proteins immobilized on fluoromicrospheres (containing the scintillant), a light signal is stimulated and measured. The application of SPA to purified, detergent-solubilized membrane transport proteins allows substrate-binding properties to be assessed (e.g., substrate specificity and affinity), usually within 1 d. Notably, the SPA makes it possible to study specific transporters without interference from other cellular components, such as endogenous transporters. Reconstitution of the target transporter into proteoliposomes is not required. The SPA procedure allows high sample throughput and simple sample handling without the need for washing or separation steps: components are mixed in one well and the signal is measured directly after incubation. Therefore, the SPA is an excellent tool for high-throughput screening experiments, e.g., to search for substrates and inhibitors, and it has also recently become an attractive tool for drug discovery.

Duration of Greenland Stadial 22 and ice-gas Δage from counting of annual layers in Greenland NGRIP ice core

High-resolution measurements of chemical impurities and methane concentrations in Greenland ice core samples from the early glacial period allow the extension of annual-layer counted chronologies and the improvement of gas age-ice age difference (Δage) essential to the synchronization of ice core records. We report high-resolution measurements of a 50 m section of the NorthGRIP ice core and corresponding annual layer thicknesses in order to constrain the duration of the Greenland Stadial 22 (GS-22) between Greenland Interstadials (GIs) 21 and 22, for which inconsistent durations and ages have been reported from Greenland and Antarctic ice core records as well as European speleothems. Depending on the chronology used, GS-22 occurred between approximately 89 (end of GI-22) and 83 kyr b2k (onset of GI-21). From annual layer counting, we find that GS-22 lasted between 2696 and 3092 years and was followed by a GI-21 pre-cursor event lasting between 331 and 369 yr. Our layer-based counting agrees with the duration of stadial 22 as determined from the NALPS speleothem record (3250 ± 526 yr) but not with that of the GICC05modelext chronology (2620 yr) or an alternative chronology based on gas-marker synchronization to EPICA Dronning Maud Land ice core. These results show that GICC05modelext overestimates accumulation and/or underestimates thinning in this early part of the last glacial period. We also revise the possible ranges of NorthGRIP Δdepth (5.49 to 5.85 m) and Δage (498 to 601 yr) at the warming onset of GI-21 as well as the Δage range at the onset of the GI-21 precursor warming (523 to 654 yr), observing that temperature (represented by the δ15N proxy) increases before CH4 concentration by no more than a few decades.

Improvement of γ-ray energy resolution of LaBr3:Ce3+ scintillation detectors by Sr2+ and Ca2+ co-doping

Commercially available LaBr3:5% Ce3+ scintillators show with photomultiplier tube readout about 2.7% energy resolution for the detection of 662 keV γ-rays. Here we will show that by co-doping LaBr3:Ce3+ with Sr2+ or Ca2+ the resolution is improved to 2.0%. Such an improvement is attributed to a strong reduction of the scintillation light losses that are due to radiationless recombination of free electrons and holes during the earliest stages (1–10 ps) inside the high free charge carrier density parts of the ionization track.