The aim of this study was to investigate the removal efficiency of six phannaceuticals by photo-degradation and the advanced oxidation process (AOP), UV/H 2O2. The six phannaceuticals were the four NSAIDs ibuprofen, diclofenac, naproxen and ketoprofen, the pharmacological active metabolite of the lipid lowering agent, clofibrin, clofibric acid, and the anticonvulsant and mood stabilizing drug, carbamazepine. Treatment experiments were perfom1ed using a UV lamp optimized for photochemical treatment in a flow through set-up. For the AOP experiments 60 mg/L H 2O2 was added to the water before treatment. The treatment effectiveness is evaluated based on the Electrical Energy per Order (EEO) (unit kWh!m\ which is defined as the electrical energy consumed per unit volume of water treated required for 90% removal of the investigated compound. It was found that four of the six phannaceuticals were completely removed in tap water by both UV treatment and the AOP. The exceptions were ibuprofen and carbamazepine, which exhibited a relationship between UV dose and removal. The electrical energy per order, EEO was detennined to 8.2 kWh/m (UV) and 3. 7 kWh/m (UV /H 2O2 ) for ibuprofen. In the wastewater effluent the removal by UV irradiation was almost complete for ketoprofen, while the other compounds show dependency of flow rate/UV dose. Ibuprofen was the compound that needed the highest UV dose to remove 90% (EEO = 33.4 kWh/m) where naproxen and clofibric acid required 9.6 kWh/m and 5.5 kWh/m , respectively. Ketoprofen and diclofenac needed considerable less energy than clofibric acid. Ibuprofen and naproxen is biodegradable and will be removed in biologically treated wastewater. Therefore, the relevant estimate of the needed treatment is the energy use for removal of clofibric acid which required 5.5 kWh/m for 90% removal.

BackgroundShedding of the Alzheimer amyloid precursor protein (APP) ectodomain can be accelerated by phorbol esters, compounds that act via protein kinase C (PKC) or through unconventional phorbol-binding proteins such as Munc13-1. We have previously demonstrated that application of phorbol esters or purified PKC potentiates budding of APP-bearing secretory vesicles at the trans-Golgi network (TGN) and toward the plasma membrane where APP becomes a substrate for enzymes responsible for shedding, known collectively as α-secretase(s). However, molecular identification of the presumptive "phospho-state-sensitive modulators of ectodomain shedding" (PMES) responsible for regulated shedding has been challenging. Here, we examined the effects on APP ectodomain shedding of four phorbol-sensitive proteins involved in regulation of vesicular membrane trafficking of APP: Munc13-1, Munc18, NSF, and Eve-1.ResultsOverexpression of either phorbol-sensitive wildtype Munc13-1 or phorbol-insensitive Munc13-1 H567K resulted in increased basal APP ectodomain shedding. However, in contrast to the report of Roßner et al (2004), phorbol ester-dependent APP ectodomain shedding from cells overexpressing APP and Munc13-1 wildtype was indistinguishable from that observed following application of phorbol to cells overexpressing APP and Munc13-1 H567K mutant. This pattern of similar effects on basal and stimulated APP shedding was also observed for Munc18 and NSF. Eve-1, an ADAM adaptor protein reported to be essential for PKC-regulated shedding of pro-EGF, was found to play no obvious role in regulated shedding of sAPPα.ConclusionOur results indicate that, in the HEK293 system, Munc13-1, Munc18, NSF, and EVE-1 fail to meet essential criteria for identity as PMES for APP.

Background and Objectives: The current intensity at which a motor response is elicited with an intraneural needle placement has been inadequately studied. We hypothesized that electrical current delivered through an intraneurally placed needle does not always result in an evoked motor response. Our secondary objective was to determine the relationship between electrical current intensity and needle-to-nerve distance. Methods: Twenty pigs were given general anesthesia and the sciatic nerves (SN) were exposed bilaterally. Electrical nerve stimulation was applied 2 cm, 1 cm, 0.5 cm, 0.2 cm, and 0.1 cm away from the SN, transepineurally, and intraneurally (in the subepineurium). Stimulation was started at 2.0 mA and decreased to the minimal current at which visible motor response was obtained. Two blinded observers agreed on the intensity and type of motor response. Specific response of SN was defined as a distal motor response (hoof twitch); nonspecific response was defined as a local muscle twitch (no hoof response). Results: At a distance of 0.5 cm to 2 cm away from the SN, only nonspecific muscle responses were observed. Specific SN responses were obtained starting at 0.1 cm away from the nerve and transepineurally with currents of 0.92 ± 0.33 mA (median 1.00 mA; range 0.24-1.48 mA) and 0.39 ± 0.33 mA (median 0.3 mA; range 0.15-1.4 mA), respectively. With the needle tip positioned intraneurally, specific motor response could be obtained at 0.56 ± 0.54 mA (median 0.3 mA; range 0.08-1.80 mA). Five (12.5%) intraneurally positioned needles only elicited a specific motor response at 0.8-1.8 mA. Conclusions: Specific response to nerve stimulation with currents <0.2 mA occurred only when the needle tip was positioned intraneurally. However, motor response could be absent with intraneural needle placement at a current intensity of up to 1.7 mA.