Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain

Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors induces strong antihyperalgesic effect during inflammatory pain. In this study we observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states. In naive animals, microglia and astrocytes expressed DPP4 protein with one and two orders of magnitude higher than neurons, respectively. DPP4 significantly increased in astrocytes during inflammation and in microglia in neuropathy. Intrathecal application of two DPP4 inhibitors tripeptide isoleucin-prolin-isoleucin (IPI) and the antidiabetic drug vildagliptin resulted in robust opioid-dependent antihyperalgesic effect during inflammation, and milder but significant opioid-independent antihyperalgesic action in the neuropathic model. The opioid-mediated antihyperalgesic effect of IPI was exclusively related to mu-opioid receptors, while vildagliptin affected mainly delta-receptor activity, although mu- and kappa-receptors were also involved. None of the inhibitors influenced allodynia. Our results suggest pathology and glia-type specific changes of DPP4 activity in the spinal cord, which contribute to the development and maintenance of hyperalgesia and interact with endogenous opioid systems

Influence of Stimulant Medication and Response Speed on Lateralization of Movement-Related Potentials in Attention-Deficit/Hyperactivity Disorder

Hyperactivity is one of the core symptoms in attention deficit hyperactivity disorder (ADHD). However, it remains unclear in which way the motor system itself and its development are affected by the disorder. Movement-related potentials (MRP) can separate different stages of movement execution, from the programming of a movement to motor post-processing and memory traces. Pre-movement MRP are absent or positive during early childhood and display a developmental increase of negativity. We examined the influences of response-speed, an indicator of the level of attention, and stimulant medication on lateralized MRP in 16 children with combined type ADHD compared to 20 matched healthy controls. We detected a significantly diminished lateralisation of MRP over the pre-motor and primary motor cortex during movement execution (initial motor potential peak, iMP) in patients with ADHD. Fast reactions (indicating increased visuo-motor attention) led to increased lateralized negativity during movement execution only in healthy controls, while in children with ADHD faster reaction times were associated with more positive amplitudes. Even though stimulant medication had some effect on attenuating group differences in lateralized MRP, this effect was insufficient to normalize lateralized iMP amplitudes.A reduced focal (lateralized) motor cortex activation during the command to muscle contraction points towards an immature motor system and a maturation delay of the (pre-) motor cortex in children with ADHD. A delayed maturation of the neuronal circuitry, which involves primary motor cortex, may contribute to ADHD pathophysiology

Adhesive method for rapidly bonded wood panel joints of prefab house construction joints

This paper covers a recently completed research project in Germany aimed at using a new rapid adhesive bonding technology in wood panel construction for modular prefabricated houses, which is an increasingly popular way of building single-family houses in Central Europe. In general, the prefabricated panels are built up by planking a frame of woodensquare ribs with particleboards. Nailing or stapling has been the main joining technique so far. A new approach was established by applying an adhesive tape based on an adhesively coated metallic carrier inserted into the joint. By connecting it to an electric power supply and heating it within a short time to the melting point, the adhesive can wet the wood andcure in the compressed joint. Different thin metallic carriers made of sheets of steel, aluminum, and brass or expanded metal were used and combined with adhesives, such as polyurethane hotmelts (PUR), PUR adhesive dispersions, andco-polyamides. Because of the requirements for structural joining in the building industry, different European Standards, such as EN 15425 [EN 15425:2008, “Adhesives—One Component Polyurethane for Load Bearing Timber Structures—Classification and Performance Requirements,” CEN-CENELEC, Brussels, Belgium, 2008], and preparation according to EN 302-1 [EN 302-1:2013, “Adhesives for Load-Bearing Timber Structures—Test Methods—Part 1: Determination of Longitudinal Tensile Shear Strength,” CEN-CENELEC, Brussels, Belgium, 2013], were discussed and implemented to find out whether a combination of squared timber, new tapes, and attached panel materials are sufficient ornot. In this paper, this new method and the material testing are introduced, from early screening for suitable adhesives to semi-sized panelspecimens in the context of the European Standards