Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

Diagnosis and Consulting for Control Network Performance Engineering of CSMA-Based Networks

Network performance engineering can verify the design and dimensioning of large-scale control networks like CSMA-based building automation networks. It combines performance analysis with diagnosis methods to evaluate the network utilization and to detect design errors before installation and can therewith save the expenses of overdimensioning and redesign. This paper will develop a diagnosis model based on fault trees that is able to use the huge amount of performance analysis results to identify design errors and analyze their coherences. This enables not only a fast tracing back of fault causes and the derivation of solutions; it can also visualize the fault coherence to the user and help him to understand his design. Additional consulting tools implement best practice strategies, to support the user in parameterization.     

A Multinomial Model of Event-Based Prospective Memory.

Prospective memory is remembering to perform an action in the future. The authors introduce the 1st formal model of event-based prospective memory, namely, a multinomial model that includes 2 separate parameters related to prospective memory processes. The 1st measures preparatory attentional processes, and the 2nd measures retrospective memory processes. The model was validated in 4 experiments. Manipulations of instructions to place importance on either the prospective memory task or the background task (Experiments 1 and 2) and manipulations of distinctiveness of prospective memory targets (Experiment 2) had expected effects on model parameters, as did a manipulation of the difficulty of prospective memory target encoding (Experiments 3 and 4). An alternative model was also evaluated. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Automated model generation for performance engineering of building automation networks

Large technical systems need to be designed both reliable and efficient. Specialized design tools offer therefore a simplified, abstract design and extend details autonomously in the background. Analytic and simulation based models could improve the quality by testing and dimensioning the design before implementation, but setting up the necessary models is time-consuming and expensive. Therefore many developers ask for analysis tools which are able to create their models from the available information in the design tools. This paper presents such an automated modeling approach basing on an existing design database at the example of a network analysis for building automation fieldbuses. The process of automated modeling is unfolded, and the potentials and limitations are discussed.     

Biotransformation of (+)-methamphetamine in fertile hen's eggs

On application of (+)-methamphetamine (1) to the albumen of embryonated hen's eggs it is possible to detect phase I as well as phase II metabolites of 1 in the allantois liquid. When application is effected on the first day of incubation, methamphetamine is less toxic than when effected on the sixth day of incubation. Besides unchanged 1 ten metabolites have been identified. Principal pathways of biotransformation are N-dealkylation as well as aromatic p-hydroxylation and--as phase II reactions--N-acetylation and other conjugation reactions. The total amount of the metabolites produced depends on time of incubation and is up to about 25% of the applied dose. Differences from, but also similarities to human metabolism have been noticed. Consequently, the experiment is likely to be suitable as an alternative method for testing biotransformation reactions.     

Machining of reproducible flaws corresponding to fatigue cracks for fracture mechanics tests of components and welded joints

In connection with the analysis and the development of failure concepts in fracture mechanics for quasistatic loaded components and elastic-plastic behaviour of the material, tests are also carried out with welded and/or complex shaped specimens or structures. Thereby the difficulty arises of generating reproducible flaws in the form of fatigue precracks in definite positions in the components, respectively in the welded joint. It is reported exemplarily about experiments on different CT25 and CCT specimens and on a pressure vessel which contained a fatigue pre-crack, a 0.2 mm saw cut or notches with notch root radius ≤ ≥ 0.1 mm as flaws. The comparison of the results with regard to J-integral at initiation of stable crack, J_i, and J_R curves shows that under certain conditions the 0.2 mm saw cut (notch root radius ≤ ≤ 0.02 mm) is a useful alternative, if reproducible generation of a fatigue pre-crack will not be successful or too expensive. The tests were carried out on StE 460 and on a welded joint of this steel at 25 ± 2°C.     

Heat-integrated reactor concepts for catalytic reforming and automotive exhaust purification

Optimal solutions in environmental catalysis require a well-coordinated development of catalysts and of process design. This contribution is devoted to energy integrated design concepts for fuel reforming and for automotive exhaust purification. The examples presented demonstrate the importance of an innovative process design for optimal utilization of existing catalysts and show the potential of future developments.

New concepts for steam reforming through the efficient coupling of the endothermic reforming reaction with an exothermic combustion reaction are discussed in the first part. These concepts have been implemented for methanol steam reforming in a counter-current reactor with distributed side feed of burner gas and for methane steam reforming in a modular reactor with a co-current reaction section for the endothermic and the combustion reaction and attached counter-current heat exchangers. Both applications employ the so-called folded sheet reactor design, which ensures an excellent heat transfer between the reforming and combustion channels and efficient heat recovery.

A similar design solution is introduced for the apparently different case of automotive exhaust purification. The proposed concept aims at decoupling exhaust after-treatment from engine control. Its main component is a counter-current heat exchanger with integrated purification stages for HC-oxidation, NO_X storage and reduction and soot filtering. A small catalytic burner at the hot end of the heat exchanger provides both heat and oxidizing or reducing agents on demand. A new soot filter design allows for safe soot filter regeneration.     

Outcome after polytrauma

BACKGROUND AND AIMS: Outcome refers to the different facets of consequences resulting from an event or intervention. These consequences may be relevant for an individual patient, but also for society. There is a growing recognition that clinical research needs to define and focus on the outcomes of medical care. Outcome research should help health care professionals to better evaluate the effectiveness of specific interventions or a therapeutic concept. This broader base of evidence should then benefit the patients. METHODS: The literature was reviewed with respect to concepts of outcome research as well as results of outcome research after major trauma. RESULTS: Measuring outcome might be relevant for research purposes as well as in daily surgical practice. In the past, clinical research in trauma care has tended to focus on survival. Mortality rates are not out, complication rates are not out, but their value is limited and restricted to given scenarios with high mortality rates. New outcomes have to be added: such a functional status, emotional health, social interaction, cognitive function, degree of disability and other indicators of health. CONCLUSION: Despite differences in injury pattern and severity of injury, there is strong evidence from the literature that the quality of life is significantly impaired after major trauma. This is true for functional outcome as well as for psycho-social outcome in up to 70% of patients.     

Polycyclic Aromatic Hydrocarbons Activate the Aryl Hydrocarbon Receptor and the Constitutive Androstane Receptor to Regulate Xenobiotic Metabolism in Human Liver Cells

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants produced by incomplete combustion of organic matter. They induce their own metabolism by upregulating xenobiotic-metabolizing enzymes such as cytochrome P450 monooxygenase 1A1 (CYP1A1) by activating the aryl hydrocarbon receptor (AHR). However, previous studies showed that individual PAHs may also interact with the constitutive androstane receptor (CAR). Here, we studied ten PAHs, different in carcinogenicity classification, for their potential to activate AHR- and CAR-dependent luciferase reporter genes in human liver cells. The majority of investigated PAHs activated AHR, while non-carcinogenic PAHs tended to activate CAR. We further characterized gene expression, protein abundancies and activities of the AHR targets CYP1A1 and 1A2, and the CAR target CYP2B6 in human HepaRG hepatoma cells. Enzyme induction patterns strongly resembled the profiles obtained at the receptor level, with AHR-activating PAHs inducing CYP1A1/1A2 and CAR-activating PAHs inducing CYP2B6. In summary, this study provides evidence that beside well-known activation of AHR, some PAHs also activate CAR, followed by subsequent expression of respective target genes. Furthermore, we found that an increased PAH ring number is associated with AHR activation as well as the induction of DNA double-strand breaks, whereas smaller PAHs activated CAR but showed no DNA-damaging potential.