Z. Biringerova, T. Buday, V. Calkovsky, B. Saniova and J. Plevkova
The Nose as a Target of Air Pollution, Physiological Aspects and Clinical Relevance of Nasal Trpa1 (Transient Receptor Potential A1) Receptors
Worldwide more than several hundred million humans are exposed to severe air pollution, and a significant part of them also smoke. The effect of air pollution on human health has been recognized for many years.
The nose, as the first portal of entry to the respiratory system is constantly exposed to a large volumes of air, which is composed of a mixture of gases, particulate matter and infectious agent, and any material other than physiological amount of oxygen, nitrogen, carbon dioxide and water is considered as pollutant. Being exposed to critical amount of air pollutants, nasal cavity shares sophisticated system of protective and defensive mechanisms regarding the lower airways and lungs, however the highest risk of direct exposure to relevant air pollutants is just within the nose. Air pollution is considered to be responsible for some of the pathological processes affecting airways prone to allergic reactions in predisposed subjects, onset of nasal sensorineural hyperresponsiveness, non-specific inflammation, sinonasal cancer and definitely, the risk is not limited just to the nasal mucosa, but can proceed toward the lower airways.
The broad spectrum of irritants probably shares very similar molecular background of action. They are capable to activate the cation channenl tranisient receptor potential A1-TRPA1 by covalent modification of the channel protein, because many of them are highly reactive and nonstable molecules with possibilities for various chemical reactions. Activation of this channel is responsible for nociceptive reactions mediated by stimulation of afferent trigeminal nerves, retrograde release of tachykinins, activation of parasympathetic afferent drive leading to increase of mucus output and decrease of nasal patency, with subsequent alteration of nasal functions. Based on the recently described neuro-immune bidirectional relationships, air pollutants may be responsible for recruitment of immune cells with infiltration of the nasal mucosa possibly leading to the inflammatory processes and allergies.
Our paper is discussing the nose as the target for air pollution, and focuses on the relevance of TRPA1 channel on trigeminal afferents in pollution mediated responses.
S. Gavliakova, J. Plevkova, J. Jakus and I. Poliacek
Methods that had been applied to study central neuronal circuits regulating cough and respiratory reflexes so far rely on recording performed in vivo, ex vivo, micro injecting and lesion methods. Based on the available data it is clear that this network is complicated, multilevel, holarchical, undergoing reconfiguration under afferent inputs. For many students and researchers it is complicated to get a virtual spatial image of these cooperating neuronal populations. The project was aimed to create graphical three-dimensional computer model of the brainstem using environment MATLAB and the matrix algebra to visualize neuron localization within the brainstem. Relevant data for the model had been taken from recent and also former research papers published in particular areas. This model may help scientists to visualize groups of neurons, help them to find targets for microinjecting or lesion studies together with stereotaxic positioning. The model is upgradeable and highly flexible for future use, research and teaching applications in MATLAB environment. MATLAB is a high-level language and interactive environment that enables you to perform computationally intensive tasks faster than with traditional programming languages
S Gavliakova, T Dolak, H Licha, S Krizova and J Plevkova
Inhalation of aromatic vapours suppressed coughing induced by citric acid (CA) in naive animals. No data are available about their effects in an animal model with primarily up-regulated cough reflex. New data indicate that aromatic vapours suppress cough via effect on nasal sensory nerves.
The aim of our study was to ascertain the efficacy of nasal application of 1,8-cineole, thymol and camphor on nasal symptoms and CA induced cough in validated model of up-regulated cough reflex. Guinea pigs (n=13) were sensitized by intraperitoneal administration of ovalbumin (OVA) and sensitization was confirmed 21 days later by skin tests. Sensitized animals were repeatedly challenged with nasal OVA to induce rhinitis, and further experiments (cough challenges) were performed during the early phase of allergic inflammation.
Cough was induced by CA in plethysmograph for 10 minutes after nasal pre-treatment with aromatic substances (10-3M) in rhinitis model. Cough was recognized from record of sudden airflow changes interrupting breathing pattern and cough sound. Final count of coughs was established by blind analysis using SonicVisualiser Software. Dose responses curves, total cough count and cough latency were analyzed.
Repeated intranasal challenge with OVA induces progressively worsening symptoms, and cough induced by CA during acute phase of allergic rhinitis was enhanced. Nasal pre-treatment with 1,8-cineole, thymol and camphor did not prevent onset of nasal symptoms, and the magnitude of symptoms was comparable to those without pretreatment. Camphor had the most potent antitussive effects (number of coughs 25±3 vs. 7±2, p<0.05) followed by thymol (number of coughs 25±3 vs. 14±2, p<0.05). The data for nasal 1,8-cineole challenge did not reach statistical significance. Cough latency followed this trend.
Although the magnitude of nasal symptoms is not influenced, the effect on cough is in case of camphor and thymol significant. Our data showed that nasal application of aromatic substances suppress citric acid induced cough in animals with up-regulated cough reflex.
Histamine is one of the most important biogenic amines and it mediates numbers of physiological processes. It is also involved in majority of inflammatory diseases via its receptors H1, H2, H3 and H4. The role of histamine had been recognized as substantial in many allergic diseases including bronchial asthma, thus the histamine receptor antagonists (H1) are frequently used in the clinical practice as potent anti-allergic and anti-inflammatory drugs. However, first generation of antihistamines have also adverse effects, predominantly sedation, changes in appetite and many more, and they are still not fully effective in all patients. Attention is now focused mainly on H3 and H4 receptor antagonists and their potential clinical applications. This review focuses basically on the H3 receptor, its expression pattern and some effects which are mediated by H3, discussing its clinical relevance