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Abstract For Solid Oxide Fuel Cells (SOFCs) to become an economically attractive energy conversion technology, suitable materials and structures which enable operation at lower temperatures, while retaining high cell performance, must be developed. Recently, the perovskite-type La 0.6 Ca 0.4 Fe 0.8 Ni 0.2 O 3 oxide has shown potential as an intermediate temperature SOFC cathode. An equivalent circuit describing the cathode polarization resistances was constructed from analyzing impedance spectra recorded at different temperatures in oxygen. A competitive electrode polarization resistance is reported for this oxygen electrode using a Ce 0.8 Gd 0.2 O 1.9 electrolyte, determined by impedance spectroscopy studies of symmetrical cells sintered at 800 °C and 1000 °C. Scanning electron microscopy (SEM) studies of the symmetrical cells revealed the absence of any reaction layer between cathode and electrolyte, and a porous electrode microstructure even when sintered at a temperature of only 800 °C. The performance of this cathode shows favorable oxygen reduction reaction (ORR) properties potentially making it an excellent choice for IT-SOFC application.

The in vitro digestion of a self nano-emulsifying drug delivery system (SNEDDS) was visualized by cryogenic transmission electron microscopy (Cryo-TEM). The dynamic lipolysis model, simulating the environment of the gastrointestinal tract in fasted conditions, was used for this purpose. The results revealed that micelles are present during the entire lipolysis process. Oil droplets from the self nano-emulsifying drug delivery system are transformed to spherical or elongated unilamellar vesicles as lipolysis progresses. Low numbers of bilamellar and open vesicles were detected. After 50% hydrolysis a decrease in the number of unilamellar vesicles and oil droplets was observed. Furthermore, the electrical properties of the oil droplets were investigated by measuring their zeta-potential values as a function of time. An increase (in absolute values) to the zeta-potential of the hydrolyzing SNEDDS droplets observed versus time implying (binding or incorporation) of the micelles to the surface. The current data emphasize that Cryo-TEM combined with the in vitro dynamic lipolysis model can offer useful information on the formation of the various colloid phases during in vitro digestion of lipid-based formulations. Furthermore, it can provide a better understanding of the in vivo behavior of these systems, as well the solubilization of lipophilic drug compounds, offering new insights for designing and optimizing oral lipid-based formulations and possibly predicting their in vivo behavior. Such methodology can be a useful tool for the strategic development of lipid-based formulations.

Serum ethanol concentrations may become higher when alcohol is consumed during treatment with histamine receptor antagonists, especially if ethanol is ingested postprandially. Only a few studies have investigated fasting subjects, and women have only been investigated sporadically.The present study compared serum ethanol concentrations after a 4-h fast followed by a low (0.15 g/kg) and a high (0.45 g/kg) dose of ethanol, on two separate occasions in six women and six men. The study was carried out before and after treatment with 400 mg cimetidine twice daily.Cimetidine administration did not change the area under the concentration-time curve or the maximal serum ethanol concentration in either women or men, irrespective of ethanol dose. Ethanol elimination rate was unchanged by cimetidine.Cimetidine does not influence the ethanol concentration-time curve when ethanol is ingested on an empty stomach.

SummaryOBJECTIVE We evaluated the long‐term results in two different groups of patients with primary hyperparathyroidism treated with ultrasonically guided percutaneous ethanol (96%) injection into parathyroid tumours.DESIGN A prospective long‐term follow‐up (more than 6 months). Ethanol (96%) was injected under ultrasonic guidance into biopsy verified solitary parathyroid tumours. Basic treatment included a maximum of three treatments with an interval of about 1 month (group 1) or 1 week (group 2). Dose of ethanol was half the volume of the parathyroid tumour.PATIENTS Two different groups of patients with only one ultrasonically detected and biopsy verified parathyroid tumour were treated. Group 1 (n= 18) were treated regardless of the severity of the hyperparathyroid disease. Group 2 (n= 14) were selected for treatment either due to severe hypercalcaemic symptoms (n= 3), a high surgical risk (n= 5), or refusal of surgery (n= 6).MEASUREMENTS The volume of the parathyroid tumours was measured as half the product of maximum length, width, and depth. Blood tests included measurements of ionized calcium, total calcium and PTH.RESULTS In group 1, 12 of 18 patients (66%) could be followed more than 6 months. Follow‐up ranged from 12 to 58 months (median 45 months). A significant decrease (P < 0 001) in serum concentrations of ionized calcium and total calcium was observed. Eight patients (44%) later underwent surgical parathyroidectomy. Injection therapy was regarded as successful in 10 of 18 patients (56%). In group 2,11 of 14 patients (79%) were followed more than 6 months. Follow‐up ranged from 18 to 50 months (median 39 months). A significant decrease (P <0 001) in serum concentrations of ionized calcium, total calcium and intact PTH (1–84) was observed. Treatment was successful in 11 of 14 patients (79%). Two patients required parathyroid surgery. Re‐examination with ultrasound showed a significant reduction in the volume of the treated parathyroid tumours. Fibrosis surrounding the parathyroid tumours was detected in eight of 10 patients who subsequently had operations. One patient from each group had a complication of a unilateral permanent vocal cord paralysis following injection therapy.CONCLUSION Partial or complete long‐term remission of primary hyperparathyroidism can be achieved using ultrasound‐guided chemical parathyroidectomy. However, the intervals between treatments should be short and the treatment should be reserved only for patients not fit for surgery.

The dynamics of porous insertion electrodes during charge or discharge is described by a simplified mathematical model, accounting for the coupled transport in electrode and electrolyte phases. A numerical method to evaluate the response of this model to either controlled potential or controlled current is outlined, and numerical results for the discharge of a porous TiS/sub 2/ electrode in an idealized organic electrolyte are presented. It is demonstrated how electrolyte depletion is the principal limiting factor in the capacity obtained during discharge of this electrode system. This depletion is a consequence of the mobility of the ions not inserted, therefore the performance or this type of electrode is optimized by choosing electrolytes with transport number as close to unity as possible for the inserted ion. 23 refs.

The substrate specificity, pH activity curves, inhibition characteristics and in vitro stabilities of the human ADH isozymes characteristic of the structural loci, ADH1, ADH2 and ADH3, have been investigated using crude tissue extracts and partially purified material. Alcohol substrates: Seventeen different alcohols were tested. The products of the three loci showed differences in their relative activities with the different substrates. Thus ADH1 isozymes were most active with ethanol, allyl alcohol, sec propanol and cyclohexanol; the 'usual' ADH2 were most active with ethanol, butanol, octanol and sec butanol; the 'atypical' ADH2 isozymes were most active with ethanol and octanol, but showed relatively low activity with butanol and Ronicol; the ADH3 isozymes were relatively very active with long straight chain primary alcohols. Aldehyde substrates: Six different aldehydes were tested. No significant differences between the isozyme products of the three loci were detected except in the case of chloral hydrate. The ADH1 and 'usual' ADH2 isozymes showed activity with chloral hydrate but this was a very poor substrate for the ADH3 and 'atypical' ADH2 isozymes. pH activity profiles: With ethanol as substrate the pH optimum for the ADH1, 'usual' ADH2 and the ADH3 isozymes was around pH 11.5 and for the 'atypical' ADH2 isozymes was about pH 8.8. With acetaldehyde as substrate the pH optima for the ADH1, 'usual' ADH2, 'atypical' ADH2 and ADH3 isozymes were about pH 8.8, 6.0, 7.0-7.5 and 6.5, resp. Inhibitors: Trichloroethanol was found to be a potent inhibitor of the ADH1 isozymes; isobutyramide an inhibitor of ADH3; and pyrazole and thiourea were shown to be powerful inhibitors of the 'atypical' ADH2 isozymes. In vitro stability: The ADH1 isozymes appeared to be relatively less stable than the 'usual' ADH2 and ADH3 isozymes. The 'atypical' ADH2 isozymes were found to be relatively very labile and particularly susceptible to freezing and thawing or storage at 10° C. The ADH 1;3 and ADH 2;3 isozymes were not demonstrably different in the properties tested.

Preclinical studies in rodents have demonstrated inhibitory effects of glucagon-like peptide-1 (GLP-1) receptor stimulation on alcohol consumption. The effects of GLP-1 receptor stimulation on alcohol intake in primates have not been investigated.We performed placebo-controlled studies on the effects of the GLP-1 receptor agonists exenatide and liraglutide on alcohol consumption in alcohol-preferring male African vervet monkeys. Monkeys selected for voluntary alcohol drinking were observed for at least 10 days of baseline drinking and allocated to drug or vehicle (n = 11-12 per group) balanced with respect to alcohol intake. Monkeys had access to alcohol 4 h/day. In a first study, monkeys were treated with exenatide 0.04 mg/kg or vehicle once weekly for 5 weeks to obtain steady-state plasma levels. In a second study, monkeys were treated daily with liraglutide (increasing dosing, 10 to 50 μg/kg/day) or vehicle over 2 weeks. In both studies, access to alcohol was suspended during drug up-titration. Then, alcohol was again made available 4 h/day and treatment was continued for 2 weeks, during which alcohol intake was recorded. Observation of alcohol intake was continued for a week of drug washout.Liraglutide and to a lesser extent exenatide significantly reduced alcohol consumption without causing any signs of emesis and with no effect on water intake as compared to vehicle.The present study demonstrates for the first time that GLP-1 receptor agonists can reduce voluntary alcohol drinking in non-human primates. The data substantiate the potential usefulness of GLP-1 receptor agonists in the treatment of alcohol use disorder.

The relative biological effectiveness (RBE) varies along the treatment field. However, in clinical practice, a constant RBE of 1.1 is assumed, which can result in undesirable side effects. This study provides an accurate overview of current clinical practice for considering proton RBE in Europe.A survey was devised and sent to all proton therapy centres in Europe that treat patients. The online questionnaire consisted of 39 questions addressing various aspects of RBE consideration in clinical practice, including treatment planning, patient follow-up and future demands.All 25 proton therapy centres responded. All centres prescribed a constant RBE of 1.1, but also applied measures (except for one eye treatment centre) to counteract variable RBE effects such as avoiding beams stopping inside or in front of an organ at risk and putting restrictions on the minimum number and opening angle of incident beams for certain treatment sites. For the future, most centres (16) asked for more retrospective or prospective outcome studies investigating the potential effect of the effect of a variable RBE. To perform such studies, 18 centres asked for LET and RBE calculation and visualisation tools developed by treatment planning system vendors.All European proton centres are aware of RBE variability but comply with current guidelines of prescribing a constant RBE. However, they actively mitigate uncertainty and risk of side effects resulting from increased RBE by applying measures and restrictions during treatment planning. To change RBE-related clinical guidelines in the future more clinical data on RBE are explicitly demanded.