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The effects of temperature and anesthetic agents on ciliary function in murine respiratory epithelia.

ABSTRACT: BACKGROUND: Mucus transport mediated by motile cilia in the airway is an important defense mechanism for prevention of respiratory infections. As cilia motility can be depressed by hypothermia or exposure to anesthetics, in this study, we investigated the individual and combined effects of dexmedetomidine (dex), fentanyl (fen), and/or isoflurane (iso) at physiologic and low temperatures on cilia motility in mouse tracheal airway epithelia. These anesthetic combinations and low temperature conditions are often used in the setting of cardiopulmonary bypass surgery, surgical repair of congenital heart disease, and cardiac intensive care. METHODS: C57BL/6J mouse tracheal epithelia were excised and cilia dynamics were captured by videomicroscopy following incubation at 15, 22-24, and 37°C with different combinations of therapeutic concentrations of dex (10?nM), fen (10?nM), and iso (0.01%). Airway ciliary motion was assessed and compared across conditions by measuring ciliary beat frequency and ciliary flow velocity. Statistical analysis was carried out using unpaired t-tests, analysis of variance, and multivariate linear regression. RESULTS: There was a linear correlation between cilia motility and temperature. Fen exerted cilia stimulatory effects, while dex and iso each had ciliodepressive effects. When added together, fen?+?iso, dex?+?iso, and dex?+?fen?+?iso were all cilia inhibitory. In contrast fenl?+?dex did not significantly alter ciliary function. CONCLUSION: We show that ciliary motility is stimulated by fen, but depressed by dex or iso. However, when used in combination, ciliary motility showed changes indicative of complex drug-drug and drug-temperature interactions not predicted by simple summation of their individual effects. Similar studies are needed to examine the human airway epithelia and its response to anesthetics.

SUBMITTER: Christopher AB

PROVIDER: S-EPMC4199259 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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The effects of temperature and anesthetic agents on ciliary function in murine respiratory epithelia.

Christopher Adam B AB Ochoa Sebastian S Krushansky Evonne E Francis Richard R Tian Xin X Zahid Maliha M Muñoz Ricardo R Lo Cecilia W CW

Frontiers in pediatrics 20141016

<h4>Background</h4>Mucus transport mediated by motile cilia in the airway is an important defense mechanism for prevention of respiratory infections. As cilia motility can be depressed by hypothermia or exposure to anesthetics, in this study, we investigated the individual and combined effects of dexmedetomidine (dex), fentanyl (fen), and/or isoflurane (iso) at physiologic and low temperatures on cilia motility in mouse tracheal airway epithelia. These anesthetic combinations and low temperature ...[more]

PMID: 25360434

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Project description:Background and Objectives: The impact of anesthetic agents on memory and cognitive function following general anesthesia is of great interest, particularly regarding their effects on the developing pediatric brain. While numerous studies have examined the relationship between anesthetic drugs and brain function, research focusing on early cognitive function following sedation remains limited. Materials and Methods: This study was a prospective, randomized controlled trial involving 148 pediatric patients scheduled for hematological procedures, specifically bone marrow aspiration (BMA) and intrathecal chemotherapy (ITC). Patients were divided into two groups based on the primary anesthetic used: the inhalational sedation group (IHG), in which sevoflurane was used, and the intravenous sedation group (IVG), which received propofol infusion. Apart from the main anesthetic agent, all sedation methods were consistent across both groups. A cognitive function test administered before sedation involved memorizing four distinct images, each associated with a different number. Then, the patients were asked to identify the omitted image upon awakening in the recovery room. Herein, this pre- vs. post-sedation test is called the early recognition assessment (ERA) tool. The primary outcome was the correct response rate after sedation for the two groups. Secondary outcomes included the sedation score, the behavior response score, and the correct response rates according to the number of sedation procedures. Results: This study included 130 patients in the final analysis, with 74 originally assigned to each group. The initial cognitive assessment revealed no significant difference in performance between the anesthetic agents. In addition, no differences were observed in the rates of correct responses or post-sedation scores after repeated procedures. However, the IVG demonstrated higher behavior response scores compared to the IHG. Conclusions: There were no significant differences in the rates of correct responses using the ERA tool between the two groups, irrespective of the number of sedation procedures performed. While some differences were noted in preoperative, intraoperative, and post-anesthesia care, these did not significantly impact the cognitive outcomes measured.

Project description:Peptide hormones and their cognate receptors belonging to neuropeptide Y (NPY) family mediate diverse biological functions in a number of tissues. Recently, we discovered the presence of the gut satiation peptide YY (PYY) in saliva of mice and humans and defined its role in the regulation of food intake and body weight maintenance. Here we report the systematic analysis of expression patterns of all NPY receptors (Rs), Y1R, Y2R, Y4R, and Y5R in lingual epithelia in mice. Using four independent assays, immunohistochemistry, in situ hybridization, immunocytochemistry and RT PCR, we show that the morphologically different layers of the keratinized stratified epithelium of the dorsal layer of the tongue express Y receptors in a very distinctive yet overlapping pattern. In particular, the monolayer of basal progenitor cells expresses both Y1 and Y2 receptors. Y1Rs are present in the parabasal prickle cell layer and the granular layer, while differentiated keratinocytes display abundant Y5Rs. Y4Rs are expressed substantially in the neuronal fibers innervating the lamina propria and mechanoreceptors. Basal epithelial cells positive for Y2Rs respond robustly to PYY(3-36) by increasing intracellular Ca(2+) suggesting their possible functional interaction with salivary PYY. In taste buds of the circumvallate papillae, some taste receptor cells (TRCs) express YRs localized primarily at the apical domain, indicative of their potential role in taste perception. Some of the YR-positive TRCs are co-localized with neuronal cell adhesion molecule (NCAM), suggesting that these TRCs may have synaptic contacts with nerve terminals. In summary, we show that all YRs are abundantly expressed in multiple lingual cell types, including epithelial progenitors, keratinocytes, neuronal dendrites and TRCs. These results suggest that these receptors may be involved in the mediation of a wide variety of functions, including proliferation, differentiation, motility, taste perception and satiation.

Project description:BackgroundMucociliary clearance (MCC) is an essential defense mechanism in airway epithelia for removing pathogens from the respiratory tract. Impaired ciliary functions and MCC have been demonstrated in asthma and chronic obstructive pulmonary disease (COPD). Long-acting muscarinic antagonists (LAMAs) are a major class of inhaled bronchodilators, which are used for treating asthma and COPD; however, the effects of LAMAs on ciliary function remain unclear. This study aimed to identify the effects of LAMAs on airway ciliary functions.MethodsWild-type BALB/c mice were treated with daily intranasal administrations of glycopyrronium for 7 days, and tracheal samples were collected. Cilia-driven flow and ciliary activity, including ciliary beat frequency (CBF), ciliary beating amplitude, effective stroke velocity, recovery stroke velocity and the ratio of effective stroke velocity to recovery stroke velocity, were analyzed by imaging techniques. Using in vitro murine models, tracheal tissues were transiently cultured in media with/without LAMAs, glycopyrronium or tiotropium, for 60 min. Cilia-driven flow and ciliary activity were then analyzed. Well-differentiated normal human bronchial epithelial (NHBE) cells were treated with glycopyrronium, tiotropium, or vehicle for 60 min, and CBF was evaluated. Several mechanistic analyses were performed.ResultsIntranasal glycopyrronium administration for 7 days significantly increased cilia-driven flow and ciliary activity in murine airway epithelium. In the murine tracheal organ culture models, treatment with glycopyrronium or tiotropium for 60 min significantly increased cilia-driven flow and ciliary activity in airway epithelium. Further, we confirmed that 60-min treatment with glycopyrronium or tiotropium directly increased CBF in well-differentiated NHBE cells. In the mechanistic analyses, neither treatment with glycopyrronium nor tiotropium affected intracellular calcium ion concentrations in well-differentiated NHBE cells. Glycopyrronium did not increase protein kinase A activity in well-differentiated NHBE cells. Moreover, glycopyrronium had no effect on extracellular adenosine triphosphate concentration.ConclusionsLAMAs exert a direct effect on airway epithelium to enhance ciliary function, which may improve impaired MCC in asthma and COPD. Further investigations are warranted to elucidate the underlying mechanisms of the effects of LAMAs on the promotion of airway ciliary function.

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The effects of temperature and anesthetic agents on ciliary function in murine respiratory epithelia.

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The effects of temperature and anesthetic agents on ciliary function in murine respiratory epithelia.

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