The chemicals between us-First results of the cluster analyses on anatomy embalming procedures in the German-speaking countries.

Hands-on courses utilizing preserved human tissues for educational training offer an important pathway to acquire basic anatomical knowledge. Owing to the reevaluation of formaldehyde limits by the European Commission, a joint approach was chosen by the German-speaking anatomies in Europe (Germany, Austria, Switzerland) to find commonalities among embalming protocols and infrastructure. A survey comprising 537 items was circulated to all anatomies in German-speaking Europe.

New aspects of neuroinflammation and neuroimmune crosstalk in the airways.

Neuroimmune interaction has long been discussed in the pathogenesis of allergic airway diseases, such as allergic asthma. Mediators released during inflammation can alter the function of both sensory and parasympathetic neurons innervating the airways. Evidence has been provided that the inflammatory response can be altered by various mediators that are released by sensory and parasympathetic neurons and vice versa.

Secondary Metabolites in Allergic Plant Pollen Samples Modulate Afferent Neurons and Murine Tracheal Rings.

Plant pollens are strong airborne elicitors of asthma. Their proteinaceous allergens have been studied intensively, but little is known about a possible contribution of pollen secondary metabolites to the nonallergic exacerbation of asthma. Pollen samples originating from 30 plant species were analyzed by HPLC coupled to PDA, ESIMS, and ELSD detectors and off-line NMR spectroscopy.

The nervous system of airways and its remodeling in inflammatory lung diseases.

Inflammatory lung diseases are associated with bronchospasm, cough, dyspnea and airway hyperreactivity. The majority of these symptoms cannot be primarily explained by immune cell infiltration. Evidence has been provided that vagal efferent and afferent neurons play a pivotal role in this regard.

Cholinergic activation of the murine trachealis muscle via non-vesicular acetylcholine release involving low-affinity choline transporters.

In addition to quantal, vesicular release of acetylcholine (ACh), there is also non-quantal release at the motor endplate which is insufficient to evoke postsynaptic responses unless acetylcholinesterase (AChE) is inhibited. We here addressed potential non-quantal release in the mouse trachea by organ bath experiments and (immuno)histochemical methods. Electrical field stimulation (EFS) of nerve terminals elicited tracheal constriction that is largely due to ACh release.

Cholinergic urethral brush cells are widespread throughout placental mammals.

We previously identified a population of cholinergic epithelial cells in murine, human and rat urethrae that exhibits a structural marker of brush cells (villin) and expresses components of the canonical taste transduction signaling cascade (α-gustducin, phospholipase Cβ2 (PLCβ2), transient receptor potential cation channel melanostatin 5 (TRPM5)). These cells serve as sentinels, monitoring the chemical composition of the luminal content for potentially hazardous compounds such as bacteria, and initiate protective reflexes counteracting further ingression. In order to elucidate cross-species conservation of the urethral chemosensory pathway we investigated the occurrence and molecular make-up of urethral brush cells in placental mammals.

The expression profile of acid-sensing ion channel (ASIC) subunits ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3 in the esophageal vagal afferent nerve subtypes.

Acid-sensing ion channels (ASICs) have been implicated in esophageal acid sensing and mechanotransduction. However, insufficient knowledge of ASIC subunit expression profile in esophageal afferent nerves hampers the understanding of their role. This knowledge is essential because ASIC subunits form heteromultimeric channels with distinct functional properties.

The neural crest- and placodes-derived afferent innervation of the mouse esophagus.

Background: The mouse is an invaluable model for mechanistic studies of esophageal nerves, but the afferent innervation of the mouse esophagus is incompletely understood. Vagal afferent neurons are derived from two embryonic sources: neural crest and epibranchial placodes. We hypothesized that both neural crest and placodes contribute to the TRPV1-positive (potentially nociceptive) vagal innervation of the mouse esophagus.

Histamine H1, H3 and H4 receptors are involved in pruritus.

Histamine has long been recognised as a classical inducer of pruritus. However, the specific mechanism of histamine-induced itch has still not been fully understood. The H1 and H4 receptor appear to be key components in the induction of itch.

Phenotypic distinctions between neural crest and placodal derived vagal C-fibres in mouse lungs.

Two major types of nociceptors have been described in dorsal root ganglia (DRGs). In comparison, little is known about the vagal nociceptor subtypes. The vagus nerves provide much of the capsaicin-sensitive nociceptive innervation to visceral tissues, and are likely to contribute to the overall pathophysiology of visceral inflammatory diseases.

Thrombin and trypsin directly activate vagal C-fibres in mouse lung via protease-activated receptor-1.

The nature of protease-activated receptors (PARs) capable of activating respiratory vagal C-fibres in the mouse was investigated. Infusing thrombin or trypsin via the trachea strongly activated vagal lung C-fibres with action potential discharge, recorded with the extracellular electrode positioned in the vagal sensory ganglion. The intensity of activation was similar to that observed with the TRPV1 agonist, capsaicin.

A Toll-like receptor 2/6 agonist reduces allergic airway inflammation in chronic respiratory sensitisation to Timothy grass pollen antigens.

Background: The hygiene hypothesis negatively correlates the microbial burden of the environment with the prevalence of T helper type 2 (Th2)-related disorders, e.g. allergy and asthma.

Expression of transforming growth factor-beta (TGF-beta) in chronic idiopathic cough.

In patients with chronic idiopathic cough, there is a chronic inflammatory response together with evidence of airway wall remodelling and an increase in airway epithelial nerves expressing TRPV-1. We hypothesised that these changes could result from an increase in growth factors such as TGFbeta and neurotrophins. We recruited 13 patients with persistent non-asthmatic cough despite specific treatment of associated primary cause(s), or without associated primary cause, and 19 normal non-coughing volunteers without cough as controls, who underwent fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsies.

CD4-positive T lymphocytes provide a neuroimmunological link in the control of adult hippocampal neurogenesis.

Adult hippocampal neurogenesis occurs in an exceptional permissive microenvironment. Neuroimmunological mechanisms might be prominently involved in the endogenous homeostatic principles that control baseline levels of adult neurogenesis. We show in this study that this homeostasis is partially dependent on CD4-positive T lymphocytes.

Therapeutic surfactants modulate the viability of eosinophils and induce inflammatory mediator release.

Background: There is increasing interest in testing surfactant preparations for asthma therapy. Previously, Curosurf was demonstrated to increase inflammation in allergic asthmatics. So far, little is known about the immunomodulatory effects of therapeutic surfactants, in particular concerning the interaction of surfactant components with eosinophils as key effector cells of the allergic airway inflammation.

TRPA1: a potential target for anti-tussive therapy.

Cough occurs as a result of the activation of specific airway sensory nerves. The mechanisms by which tussive stimuli activate these sensory nerves are starting to be understood and suggest that TRPA1 channels are heavily involved. TRPA1 channels are nociceptor-specific ion channels that are gated by a wide range of exogenous irritants and endogenously-produced inflammatory mediators, suggesting that the blockade of TRPA1 represents a novel therapy for the treatment of cough in humans.

Airway nerves and dyspnea associated with inflammatory airway disease.

The neurobiology of dyspnea is varied and complex, but there is little doubt that vagal nerves within the airways are capable of causing or modulating some dyspneic sensations, especially those associated with inflammatory airway diseases. A major contributor to the dyspnea associated with inflammatory airway disease is explained by airway narrowing and increases in the resistance to airflow. The autonomic (parasympathetic) airway nerves directly contribute to this by regulating bronchial smooth muscle tone and mucus secretion.

P2X2 receptors differentiate placodal vs. neural crest C-fiber phenotypes innervating guinea pig lungs and esophagus.

The lungs and esophagus are innervated by sensory neurons with somata in the nodose, jugular, and dorsal root ganglion. These sensory ganglia are derived from embryonic placode (nodose) and neural crest tissues (jugular and dorsal root ganglia; DRG). We addressed the hypothesis that the neuron's embryonic origin (e.

Leukotriene D4 increases the excitability of capsaicin-sensitive nasal sensory nerves to electrical and chemical stimuli.

Background And Purpose: Clinical studies have demonstrated significant reductions in allergen-induced nasal symptoms of atopic rhinitis subjects by CysLT1 antagonists, including neuronally mediated symptoms such as sneeze, itch and reflex hypersecretion. Here, we test the hypothesis that cysteinyl leukotrienes activate and/or alter the activity of nasal nociceptive (capsaicin-sensitive) sensory neurones.

Experimental Approach: Using retrograde tracer (DiI), we labelled guinea-pig trigeminal sensory neurones that projected fibres to the nasal mucosa.

Relative contributions of TRPA1 and TRPV1 channels in the activation of vagal bronchopulmonary C-fibres by the endogenous autacoid 4-oxononenal.

Transient receptor potential (TRP) A1 channels are cation channels found preferentially on nociceptive sensory neurones, including capsaicin-sensitive TRPV1-expressing vagal bronchopulmonary C-fibres, and are activated by electrophilic compounds such as mustard oil and cinnamaldehyde. Oxidative stress, a pathological feature of many respiratory diseases, causes the endogenous formation of a number of reactive electrophilic alkenals via lipid peroxidation. One such alkenal, 4-hydroxynonenal (4HNE), activates TRPA1 in cultured sensory neurones.

Expression and function of the ion channel TRPA1 in vagal afferent nerves innervating mouse lungs.

Transient receptor potential (TRP) A1 and TRPM8 are ion channels that have been localized to afferent nociceptive nerves. These TRP channels may be of particular relevance to respiratory nociceptors in that they can be activated by various inhaled irritants and/or cold air. We addressed the hypothesis that mouse vagal sensory nerves projecting to the airways express TRPA1 and TRPM8 and that they can be activated via these receptors.

Neuroimmune crosstalk in asthma: dual role of the neurotrophin receptor p75NTR.

Background: Neurotrophins have been implicated in the pathogenesis of asthma because of their ability to induce airway inflammation and to promote hyperreactivity of sensory neurons, which reflects an important mechanism in the pathogenesis of airway hyperreactivity. Neurotrophins use a dual-receptor system consisting of Trk-receptor tyrosine kinases and the structurally unrelated p75NTR. Previous studies revealed an important role of p75NTR in the pathogenesis of allergic asthma.

Spatial interactions between dendritic cells and sensory nerves in allergic airway inflammation.

Neuroimmune interactions play a critical role in the pathogenesis of asthma. Symptoms like wheezing and cough have been attributed to neural dysregulation, whereas sensitization and the induction of allergic inflammation have been linked with the activity of dendritic cells. Neuropeptides were previously shown to control dendritic cell function in vitro, suggesting interactions between dendritic cells and sensory nerves.

Strain-dependent resistance to allergen-induced lung pathophysiology in mice correlates with rate of apoptosis of lung-derived eosinophils.

Although exposed to similar allergic and environmental stimuli, not all humans develop asthma. Similarly, mouse strains vary in the degree of pathophysiology seen following induction of experimental asthma. Three mouse strains (CBA/Ca, BALB/c, and C57BL/6) were used to determine if the extent and duration of inflammation influenced the degree of lung tissue damage in an OVA-induced allergic asthma model.