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Cholecystokinin-tetrapeptide (CCK-4) induces panic attacks both in patients with panic disorder (PD) and healthy volunteers. It has been shown that panic elicited by CCK-4 is improved after treatment with antidepressants. Moreover, a reduction of CCK-4-induced panic has also been demonstrated after treatment with lorazepam in single subjects and after selective GABAergic treatment with vigabatrin. Although benzodiazepines are widely used as anxiolytics, no controlled study on the effects of benzodiazepines on CCK-4-induced panic symptoms is available so far. Therefore, we investigated the effects of alprazolam and placebo on CCK-4-induced panic symptoms in a double-blind, placebo-controlled study. A total of 30 healthy subjects were challenged with 50 µg CCK-4. Out of these 30 subjects, 26 showed a marked panic response to CCK-4. Subjects were rechallenged after a 7-day interval and treated with 1 mg alprazolam or placebo 1 h prior to the second CCK-4 challenge. Panic was assessed using the acute panic inventory (API) and a DSM-IV-derived panic symptom scale (PSS). Moreover, the number of reported symptoms and self-rated anxiety and arousal were recorded. We found a significant reduction of the API and PSS scores and of the number of reported symptoms compared to placebo. Moreover, compared to placebo the CCK-4-induced ACTH and cortisol release were significantly attenuated during the CCK-4 challenge after alprazolam treatment. However, also placebo treatment reduced CCK-4-induced anxiety and HPA-axis activation to a certain extent. In conclusion, our data show that alprazolam reduces CCK-4-induced panic, which supports the hypothesis of a possible interaction between the GABA and the CCK system. [ABSTRACT FROM AUTHOR]

The solitary tract nucleus (NTS) conveys visceral information to diverse central networks involved in homeostatic regulation. Although afferent information content arriving at various CNS sites varies substantially, little is known about the contribution of processing within the NTS to these differences. Using retrograde dyes to identify specific NTS projection neurons, we recently reported that solitary tract (ST) afferents directly contact NTS neurons projecting to caudal ventrolateral medulla (CVLM) but largely only indirectly contact neurons projecting to the hypothalamic paraventricular nucleus (PVN). Since intrinsic properties impact information transmission, here we evaluated potassium channel expression and somatodendritic morphology of projection neurons and their relation to afferent information output directed to PVN or CVLM pathways. In slices, tracer-identified projection neurons were classified as directly or indirectly (polysynaptically) coupled to ST afferents by EPSC latency characteristics (directly coupled, jitter < 200 μs). In each neuron, voltage-dependent potassium currents (IK) were evaluated and, in representative neurons, biocytin-filled structures were quantified. Both CVLM- and PVN-projecting neurons had similar, tetraethylammonium-sensitive IK. However, only PVN-projecting NTS neurons displayed large transient, 4aminopyridine-sensitive, A-type currents (IKA). PVN-projecting neurons had larger cell bodies with more elaborate dendritic morphology than CVLM-projecting neurons. ST shocks faithfully (> 75%) triggered action potentials in CVLM-projecting neurons but spike output was uniformly low (< 20%) in PVN-projecting neurons. Pre-conditioning hyperpolarization removed IKA inactivation and attenuated ST-evoked spike generation along PVN but not CVLM pathways. Thus, multiple differences in structure, organization, synaptic transmission and ion channel expression tune the overall fidelity of afferent signals that reach these destinations. [ABSTRACT FROM AUTHOR]

Abstract: Cellulose fiber reinforced gypsum based materials are gaining increasing importance in the building industry. The non-combustible panel material is produced in thicknesses of 10–40mm and with a fiber content of about 20vol.%. The fiber orientation in the composite is predominantly random planar. A major application for the panels is sheathing and bracing of timber frame wall elements. The material exhibits a macroscopic response that resembles that of a ductile material with pronounced strain softening. These material characteristics, which deliver high energy dissipation especially during reversed cyclic loading, are advantageous for seismically loaded structures. In this paper the homogenized fracture behavior for this material is described for the first time for static and quasi-static cyclic loading using a Plastic-Damage model proposed by [J. Lubliner, J. Oliver, S. Oller, E. Oñate, Int. J. Solids and Structures 25, 3 (1989), 229–326, J. Lee, G. L. Fenves, J. Eng. Mech. 124, 8 (1998), 892–900]. This model is primarily used to simulate quasi-brittle materials such as concrete, rock, mortar and ceramics. The model input parameters such as tensile strength and fracture energy are obtained from uniaxial test results. The numerical simulations have been performed with ABAQUS. The different features and parameters of the applied Plastic-Damage model are discussed with respect to their capability to describe the behavior of cellulose fiber reinforced gypsum. [Copyright &y& Elsevier]

This paper reports on a combined experimental and theoretical study on the size dependency of tension strength of clear wood at loading parallel to fiber direction. The fracture behavior of the tested softwood specimens was found to be rather brittle with low precursory activity and a statistical variation of the strength. The distribution of the strength values can be well fitted with a Weibull distribution distinguished by a shape parameter ρ∼8−10. A significant dependency of the mean strength of the material on the cross-sectional size of the specimens was obtained. The range of load redistribution in clear wood subjected to tension parallel to fiber was assessed by the theoretical concept of fiber bundle models for fiber composites. Hereby the macroscopic behavior was modelled in terms of the microscopic damage process. [Copyright &y& Elsevier]