Relationship between tendon structure, stiffness, gait patterns and patient reported outcomes during the early stages of recovery after an Achilles tendon rupture.

After an Achilles tendon (AT) injury, the decision to return to full weightbearing for the practice of sports or strenuous activities is based on clinical features only. In this study, tendon stiffness and foot plantar pressure, as objective quantitative measures that could potentially inform clinical decision making, were repeatedly measured in 15 patients until 3 months after the AT rupture by using shear wave elastography (SWE) and wearable insoles, respectively. Meanwhile, patient reported outcomes assessing the impact on physical activity were evaluated using the Achilles Tendon Total Rupture Score (ATRS).

AQW051, a novel, potent and selective α7 nicotinic ACh receptor partial agonist: pharmacological characterization and phase I evaluation.

Background And Purpose: Activation of the α7 nicotinic ACh receptor (nACh receptor) is considered an attractive target for the treatment of cognitive impairment associated with neurological disorders. Here we describe the novel α7-nACh receptor agonist AQW051 as a promising drug candidate for this indication.

Experimental Approach: AQW051 was functionally characterized in vitro and cognitive effects evaluated in rodent behavioural models.

Differential roles of mGlu(7) and mGlu(8) in amygdala-dependent behavior and physiology.

Glutamate transmission and synaptic plasticity in the amygdala are essential for the learning and expression of conditioned fear. Glutamate activates both ionotropic glutamate receptors and eight subtypes of metabotropic glutamate receptors (mGlu1-8). In the present study, we investigated the roles of mGlu7 and mGlu8 in amygdala-dependent behavior and synaptic plasticity.

Gastrin-releasing peptide signaling plays a limited and subtle role in amygdala physiology and aversive memory.

Links between synaptic plasticity in the lateral amygdala (LA) and Pavlovian fear learning are well established. Neuropeptides including gastrin-releasing peptide (GRP) can modulate LA function. GRP increases inhibition in the LA and mice lacking the GRP receptor (GRPR KO) show more pronounced and persistent fear after single-trial associative learning.

Characterization of a novel, brain-penetrating CB1 receptor inverse agonist: metabolic profile in diet-induced obese models and aspects of central activity.

Pharmacologic antagonism of cannabinoid 1 receptors (CB1 receptors) in the central nervous system (CNS) suppresses food intake, promotes weight loss, and improves the metabolic profile. Since the CB1 receptor is expressed both in the CNS and in peripheral tissues, therapeutic value may be gained with CB1 receptor inverse agonists acting on receptors in both domains. The present report examines the metabolic and CNS actions of a novel CB1 receptor inverse agonist, compound 64, a 1,5,6-trisubstituted pyrazolopyrimidinone.

Fear-reducing effects of intra-amygdala neuropeptide Y infusion in animal models of conditioned fear: an NPY Y1 receptor independent effect.

Rationale: Neuropeptide Y (NPY) and its receptors are densely localized in brain regions involved in the mediation and modulation of fear, including the amygdala. Several studies showed that central NPY is involved in the modulation of fear and anxiety.

Objectives: In the present study, we investigated (1) whether intra-amygdala injections of NPY affect the expression of conditioned fear and (2) whether NPY Y1 receptors (Y1R) mediates the effects of these intra-amygdaloid NPY injections.

Translocator protein (18 kD) as target for anxiolytics without benzodiazepine-like side effects.

Most antianxiety drugs (anxiolytics) work by modulating neurotransmitters in the brain. Benzodiazepines are fast and effective anxiolytic drugs; however, their long-term use is limited by the development of tolerance and withdrawal symptoms. Ligands of the translocator protein [18 kilodaltons (kD)] may promote the synthesis of endogenous neurosteroids, which also exert anxiolytic effects in animal models.

The selective nicotinic acetylcholine receptor alpha7 agonist JN403 is active in animal models of cognition, sensory gating, epilepsy and pain.

Several lines of evidence suggest that the nicotinic acetylcholine receptor alpha7 (nAChR alpha7) is involved in central nervous system disorders like schizophrenia and Alzheimer's disease as well as in inflammatory disorders like sepsis and pancreatitis. The present article describes the in vivo effects of JN403, a compound recently characterized to be a potent and selective partial nAChR alpha7 agonist. JN403 rapidly penetrates into the brain after i.

Behavioral characterization of the novel GABAB receptor-positive modulator GS39783 (N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine): anxiolytic-like activity without side effects associated with baclofen or benzodiazepines.

The role of GABAB receptors in various behavioral processes has been largely defined using the prototypical GABAB receptor agonist baclofen. However, baclofen induces sedation, hypothermia and muscle relaxation, which may interfere with its use in behavioral paradigms. Although there is much evidence for a role of the inhibitory neurotransmitter GABA in the pathophysiology of anxiety, the role of GABAB receptors in these disorders is largely unclear.

Effects of a dopamine D3 receptor ligand, BP 897, on acquisition and expression of food-, morphine-, and cocaine-induced conditioned place preference, and food-seeking behavior in rats.

The present study addressed the role of dopaminergic D(3) receptors (D(3)R) in motivational processes in rats. The effects of the selective D(3)R partial agonist, BP 897 (0.25-1 mg/kg, i.