scholarly journals Involvement of Capsaicin-Sensitive Lung Vagal Neurons and TRPA1 Receptors in Airway Hypersensitivity Induced by 1,3-β-D-Glucan in Anesthetized Rats

2020 ◽  
Vol 21 (18) ◽  
pp. 6845
Author(s):  
You Shuei Lin ◽  
I-Hsuan Huang ◽  
Sheng-Hsuan Lan ◽  
Chia-Ling Chen ◽  
Yueh-Yin Chen ◽  
...  
Keyword(s):  
Pulmonary Inflammation ◽  
Intratracheal Instillation ◽  
Pathogenic Fungi ◽  
Vital Role ◽  
Irregular Pattern ◽  
Marked Enhancement ◽  
Ros Scavenger ◽  
Airway Hypersensitivity ◽  
Spontaneously Breathing

Airway exposure to 1,3-β-D-glucan (β-glucan), an essential component of the cell wall of several pathogenic fungi, causes various adverse responses, such as pulmonary inflammation and airway hypersensitivity. The former response has been intensively investigated; however, the mechanism underlying β-glucan-induced airway hypersensitivity is unknown. Capsaicin-sensitive lung vagal (CSLV) afferents are very chemosensitive and stimulated by various insults to the lungs. Activation of CSLV afferents triggers several airway reflexes, such as cough. Furthermore, the sensitization of these afferents is known to contribute to the airway hypersensitivity during pulmonary inflammation. This study was carried out to determine whether β-glucan induces airway hypersensitivity and the role of the CSLV neurons in this hypersensitivity. Our results showed that the intratracheal instillation of β-glucan caused not only a distinctly irregular pattern in baseline breathing, but also induced a marked enhancement in the pulmonary chemoreflex responses to capsaicin in anesthetized, spontaneously breathing rats. The potentiating effect of β-glucan was found 45 min later and persisted at 90 min. However, β-glucan no longer caused the irregular baseline breathing and the potentiating of pulmonary chemoreflex responses after treatment with perineural capsaicin treatment that blocked the conduction of CSLV fibers. Besides, the potentiating effect of β-glucan on pulmonary chemoreflex responses was significantly attenuated by N-acetyl-L-cysteine (a ROS scavenger), HC-030031 (a TRPA1 antagonist), and Laminarin (a Dectin-1 antagonist). A combination of Laminarin and HC-030031 further reduced the β-glucan-induced effect. Indeed, our fiber activity results showed that the baseline fiber activity and the sensitivity of CSLV afferents were markedly elevated by β-glucan instillation, with a similar timeframe in anesthetized, artificially ventilated rats. Moreover, this effect was reduced by treatment with HC-030031. In isolated rat CSLV neurons, the β-glucan perfusion caused a similar pattern of potentiating effects on capsaicin-induced Ca2+ transients, and β-glucan-induced sensitization was abolished by Laminarin pretreatment. Furthermore, the immunofluorescence results showed that there was a co-localization of TRPV1 and Dectin-1 expression in the DiI-labeled lung vagal neurons. These results suggest that CSLV afferents play a vital role in the airway hypersensitivity elicited by airway exposure to β-glucan. The TRPA1 and Dectin-1 receptors appear to be primarily responsible for generating β-glucan-induced airway hypersensitivity.

scholarly journals Influence of DMT1 and iron status on inflammatory responses in the lung

2011 ◽  
Vol 300 (4) ◽  
pp. L659-L665 ◽  
Author(s):  
Jonghan Kim ◽  
Ramon M. Molina ◽  
Thomas C. Donaghey ◽  
Peter D. Buckett ◽  
Joseph D. Brain ◽  
...  
Keyword(s):  
Lung Injury ◽  
Inflammatory Responses ◽  
Iron Status ◽  
Pulmonary Inflammation ◽  
Intratracheal Instillation ◽  
Cell Content ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter

Divalent metal transporter 1 (DMT1) is the major iron transporter responsible for duodenal dietary iron absorption and is required for erythropoiesis. Recent studies suggest that loss of DMT1 activity could be involved in metal-related lung injury, but little is known about the effects of iron status and DMT1 function on pulmonary inflammation. To better define the role of DMT1 and iron status in pulmonary inflammatory responses, we performed bronchoalveolar lavage (BAL) following intratracheal instillation of lipopolysaccharide (LPS) to the Belgrade rat, an animal model deficient in DMT1 function. In the basal state, the BAL fluid of Belgrade rats had more macrophages and higher lactate dehydrogenase, myeloperoxidase, albumin, and hemoglobin levels compared with heterozygote control rats. Following LPS instillation, the macrophage fraction relative to total BAL cell content and levels of albumin and IgM were increased in Belgrade rats compared with controls. In contrast, heterozygote Belgrade rats made anemic by diet-induced iron deficiency exhibited attenuated inflammatory responses to LPS. These combined results show that pulmonary inflammation can be modified by both DMT1 and iron status. Loss of DMT1 alters pulmonary responses necessary for lung homeostasis in the basal state and enhances LPS-induced inflammation and therefore would contribute to progression of lung injury.

scholarly journals Hypersensitivity of Airway Reflexes Induced by Hydrogen Sulfide: Role of TRPA1 Receptors

2020 ◽  
Vol 21 (11) ◽  
pp. 3929
Author(s):  
Chi-Li Chung ◽  
You Shuei Lin ◽  
Nai-Ju Chan ◽  
Yueh-Yin Chen ◽  
Chun-Chun Hsu
Keyword(s):  
Hydrogen Sulfide ◽  
Enhancement Effect ◽  
Sodium Hydrosulfide ◽  
Cough Reflex ◽  
Functional Changes ◽  
Intracerebroventricular Infusion ◽  
Airway Reflex ◽  
Airway Hypersensitivity ◽  
Spontaneously Breathing

The activation of capsaicin-sensitive lung vagal (CSLV) afferents can elicit airway reflexes. Hypersensitivity of these afferents is known to contribute to the airway hypersensitivity during airway inflammation. Hydrogen sulfide (H2S) has been suggested as a potential therapeutic agent for airway hypersensitivity diseases, such as asthma, because of its relaxing effect on airway smooth muscle and anti-inflammatory effect. However, it is still unknown whether H2S affects airway reflexes. Our previous study demonstrated that exogenous application of H2S sensitized CSLV afferents and enhanced Ca2+ transients in CSLV neurons. The present study aimed to determine whether the H2S-induced sensitization leads to functional changes in airway reflexes and elevates the electrical excitability of the CSLV neurons. Our results showed that, first and foremost, in anesthetized, spontaneously breathing rats, the inhalation of aerosolized sodium hydrosulfide (NaHS, a donor of H2S; 5 mg/mL, 3 min) caused an enhancement in apneic response evoked by several stimulants of the CSLV afferents. This enhancement effect was found 5 min after NaHS inhalation and returned to control 30 min later. However, NaHS no longer enhanced the apneic response after perineural capsaicin treatment on both cervical vagi that blocked the conduction of CSLV fibers. Furthermore, the enhancing effect of NaHS on apneic response was totally abolished by pretreatment with intravenous HC-030031 (a TRPA1 antagonist; 8 mg/kg), whereas the potentiating effect was not affected by the pretreatment with the vehicle of HC-030031. We also found that intracerebroventricular infusion pretreated with HC-030031 failed to alter the potentiating effect of NaHS on the apneic response. Besides, the cough reflex elicited by capsaicin aerosol was enhanced by inhalation of NaHS in conscious guinea pigs. Nevertheless, this effect was entirely eliminated by pretreatment with HC-030031, not by its vehicle. Last but not least, voltage-clamp electrophysiological analysis of isolated rat CSLV neurons showed a similar pattern of potentiating effects of NaHS on capsaicin-induced inward current, and the involvement of TRPA1 receptors was also distinctly shown. In conclusion, these results suggest that H2S non-specifically enhances the airway reflex responses, at least in part, through action on the TRPA1 receptors expressed on the CSLV afferents. Therefore, H2S should be used with caution when applying for therapeutic purposes in airway hypersensitivity diseases.

Role of C fibers in the inflammatory response to intratracheal lipopolysaccharide

1996 ◽  
Vol 271 (3) ◽  
pp. L425-L431 ◽  
Author(s):  
N. C. Long ◽  
C. W. Frevert ◽  
S. A. Shore
Keyword(s):  
Inflammatory Response ◽  
Alveolar Macrophages ◽  
Tumor Necrosis ◽  
Pulmonary Inflammation ◽  
Intratracheal Instillation ◽  
C Fibers ◽  
Vehicle Treatment ◽  
Necrosis Factor

We proposed that C fibers play a role in mediating the inflammatory response to the intratracheal instillation of lipopolysaccharaide (LPS), a purified form of endotoxin. To test this hypothesis, we compared the inflammatory response to intratracheal LPS (0.1-2.5 mg/kg) in rats whose C fibers had been destroyed by neonatal capsaicin treatment to the response seen in animals that were treated with vehicle. Three hours after the instillation of LPS, we assessed pulmonary inflammation by performing bronchoalveolar lavage (BAL) on the animals. We measured the number of neutrophils, the concentration of protein as an index of vascular permeability, and the concentration of tumor necrosis factor (TNF). Our results indicate that capsaicin treatment resulted in more neutrophils and higher levels of protein and TNF in the BAL fluid in response to intratracheal LPS, compared with vehicle treatment. Using cells from both groups of rats, we also assessed the production of inflammatory mediators by alveolar macrophages incubated with LPS (0.3-30 ng/ml) in vitro. We found a modest increase in the concentration of TNF and nitrite in the supernatant of macrophages collected from capsaicin-treated rats, in comparison with vehicle-treated animals. These results are consistent with the hypothesis that intrinsic differences in the sensitivity of alveolar macrophages of capsaicin and vehicle-treated animals contribute to the greater inflammatory response of capsaicin-treated rat to intratracheal LPS.

scholarly journals FAM134B-Mediated ER-phagy Upregulation Attenuates AGEs-Induced Apoptosis and Senescence in Human Nucleus Pulposus Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Rongjin Luo ◽  
Shuai Li ◽  
Gaocai Li ◽  
Saideng Lu ◽  
Weifeng Zhang ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Intervertebral Disc Degeneration ◽  
Vital Role ◽  
Nucleus Pulposus Cells ◽  
Ros Accumulation ◽  
Intracellular Ros ◽  
Glycation End Products ◽  
Ros Scavenger ◽  
Induced Apoptosis

Previous studies have established the pathogenic role of advanced glycation end products (AGEs) accumulation in intervertebral disc degeneration (IDD). Emerging evidence indicates that ER-phagy serves as a crucial cellular adaptive mechanism during stress conditions. This study is aimed at investigating the role of FAM134B-mediated ER-phagy in human nucleus pulposus (NP) cells upon AGEs treatment and exploring its regulatory mechanisms. We observed that AGEs treatment resulted in significantly increased apoptosis, senescence, and ROS accumulation in human NP cells; meanwhile, the enhanced apoptosis and senescence by AGEs treatment could be partially alleviated with the classic ROS scavenger NAC administration. Furthermore, we confirmed that FAM134B-mediated ER-phagy was activated under AGEs stimulation via ROS pathway. Importantly, it was also found that FAM134B overexpression could efficiently relieve intracellular ROS accumulation, apoptosis, and senescence upon AGEs treatment; conversely, FAM134B knockdown markedly resulted in opposite effects. In conclusion, our data demonstrate that FAM134B-mediated ER-phagy plays a vital role in AGEs-induced apoptosis and senescence through modulating cellular ROS accumulation, and targeting FAM134B-mediated ER-phagy could be a promising therapeutic strategy for IDD treatment.

Asiana Airlines Flight 214

2014 ◽  
Vol 4 (2) ◽  
pp. 113-121 ◽  
Author(s):  
Stephanie Chow ◽  
Stephen Yortsos ◽  
Najmedin Meshkati
Keyword(s):  
Human Factors ◽  
Aviation Safety ◽  
Cultural Factors ◽  
Vital Role ◽  
Cultural Issues ◽  
Flight Crew ◽  
Pilot Performance ◽  
Engineering Designs ◽  
Flight Deck

This article focuses on a major human factors–related issue that includes the undeniable role of cultural factors and cockpit automation and their serious impact on flight crew performance, communication, and aviation safety. The report concentrates on the flight crew performance of the Boeing 777–Asiana Airlines Flight 214 accident, by exploring issues concerning mode confusion and autothrottle systems. It also further reviews the vital role of cultural factors in aviation safety and provides a brief overview of past, related accidents. Automation progressions have been created in an attempt to design an error-free flight deck. However, to do that, the pilot must still thoroughly understand every component of the flight deck – most importantly, the automation. Otherwise, if pilots are not completely competent in terms of their automation, the slightest errors can lead to fatal accidents. As seen in the case of Asiana Flight 214, even though engineering designs and pilot training have greatly evolved over the years, there are many cultural, design, and communication factors that affect pilot performance. It is concluded that aviation systems designers, in cooperation with pilots and regulatory bodies, should lead the strategic effort of systematically addressing the serious issues of cockpit automation, human factors, and cultural issues, including their interactions, which will certainly lead to better solutions for safer flights.

On The Mechanism Of Heparin-Induced Potentiation Of Platelet Aggregation

1981 ◽  
Author(s):  
M Yamamoto ◽  
K Watanabe ◽  
Y Ando ◽  
H Iri ◽  
N Fujiyama ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Coagulation Factors ◽  
Marked Enhancement ◽  
Matrix Bound ◽  
Induced Aggregation ◽  
Aggregation Of Platelets ◽  
Plasma Heparin

It has been suggested that heparin caused potentiation of aggregation induced by ADP or epinephrine. The exact mechanism of heparin-induced platelet activation, however, remained unknown. In this paper, we have investigated the role of anti-thrombin III ( AT ) in heparin-induced platelet activation using purified AT and AT depleted plasma. When ADP or epinephrine was added to citrated PRP one minute after addition of heparin ( 1 u/ml, porcine intestinal mucosal heparin, Sigma Co. USA ), marked enhancement of platelet aggregation was observed, compared with the degree of aggregation in the absence of heparin. However, in platelet suspensions prepared in modified Tyrode’s solution, heparin exhibited no potentiating effect on platelet aggregation induced by epinephrine or ADP. Potentiation of epinephrine- or ADP-induced platelet aggregation by heparin was demonstrated when purified AT was added to platelet suspensions at a concentration of 20 μg/ml. AT depleted plasma, which was prepared by immunosorption using matrix-bound antibodies to AT, retained no AT, while determination of α1-antitrypsinα2- macroglobulin and fibrinogen in AT depleted plasma produced values which corresponded to those of the original plasma when dilution factor was taken into account. The activities of coagulation factors were also comparable to those of the original plasma. Heparin exhibited potentiating effect on ADP- or epinephrine-induced aggregation of platelets in original plasma, but no effect in AT depleted plasma. When purified AT was added back to AT depleted plasma at a concentration of 20 μg/ml, potentiation of platelet aggregation by heparin was clearly demonstrated.Our results suggest that effect of heparin on platelet aggregation is also mediated by anti-thrombin III.

Energy Efficiency Analysis in ERA using NFL-BA Algorithm

2020 ◽  
pp. 340-348
Author(s):  
Palky Mehta ◽  
H. L. Sharma
Keyword(s):  
Cluster Head ◽  
Vital Role ◽  
Wireless Sensor ◽  
Energy Usage ◽  
Cluster Heads ◽  
Comparison Results ◽  
Current Scenario ◽  
Energy Efficiency Analysis ◽  
Selection Of

In the current scenario of Wireless Sensor Network (WSN), power consumption is the major issue associated with nodes in WSN. LEACH technique plays a vital role of clustering in WSN and reduces the energy usage effectively. But LEACH has its own limitation in order to search cluster head nodes which are randomly distributed over the network. In this paper, ERA-NFL- BA algorithm is being proposed for selects the cluster heads in WSN. This algorithm help in selection of cluster heads can freely transform from global search to local search. At the end, a comparison has been done with earlier researcher using protocol ERA-NFL, which clearly shown that proposed Algorithm is best suited and from comparison results that ERA-NFL-BA has given better performance.

Tertiary English-majored Students’ Perceptions toward the Role of Pronunciation in English Language Learning and their Practicing Strategies

2020 ◽  
Vol 6 (2) ◽  
pp. 264-279
Keyword(s):  
Language Learning ◽  
English Language ◽  
Vital Role ◽  
English Language Learning ◽  
Structured Interviews ◽  
Efl Learners ◽  
The University

Accurate pronunciation has a vital role in English language learning as it can help learners to avoid misunderstanding in communication. However, EFL learners in many contexts, especially at the University of Phan Thiet, still encounter many difficulties in pronouncing English correctly. Therefore, this study endeavors to explore English-majored students’ perceptions towards the role of pronunciation in English language learning and examine their pronunciation practicing strategies (PPS). It involved 155 English-majored students at the University of Phan Thiet who answered closed-ended questionnaires and 18 English-majored students who participated in semi-structured interviews. The findings revealed that students strongly believed in the important role of pronunciation in English language learning; however, they sometimes employed PPS for their pronunciation improvement. Furthermore, the results showed that participants tended to use naturalistic practicing strategies and formal practicing strategies with sounds, but they overlooked strategies such as asking for help and cooperating with peers. Such findings could contribute further to the understanding of how students perceive the role of pronunciation and their PPS use in the research’s context and other similar ones. Received 10th June 2019; Revised 12th March 2020; Accepted 12th April 2020

The role of Record of Rights (Khatian) in determining title or possession: An overview

IIUC Studies ◽  
2020 ◽  
Vol 15 ◽  
pp. 33-46
Author(s):  
Kalim Ullah
Keyword(s):  
Human Life ◽  
Vital Role ◽  
Critical Element ◽  
Human Beings ◽  
Supportive Evidence ◽  
Land Administration ◽  
Holy Quran ◽  
The Holy Quran ◽  
Religious Systems

Human beings are deeply related to land. Human beings take birth on land, live on land, die on land and mixes with land ultimately. As stated in the holy Quran: ‘We (Allah) created you (human beings) from the soil, we shall make you return to the soil and We shall call you back again from the soil’ (20:55). Human life is surrounded by soil i.e. land. So, land is a highly completed issue of human life involving economic, social, political, cultural and often religious systems. Land administration is thus a critical element and often a pre-condition for peaceful society and sustainable development. In administrating land, Khatian or record of rights plays a vital role to determine the rights and interests of the respective parties as supportive evidence. In this article, discussion is mainly made on the fact that Khatian or record of rights is not a document of title solely but it may be an evidence of title as well as possession. IIUC Studies Vol.15(0) December 2018: 33-46

A Court in Decline? Examining the Regality Court Records of Melrose, Roxburghshire, 1657–84

2020 ◽  
Vol 40 (1) ◽  
pp. 1-16
Author(s):  
Vivienne Dunstan
Keyword(s):  
Seventeenth Century ◽  
Local Community ◽  
Local Population ◽  
Local Area ◽  
Vital Role ◽  
Local Communities ◽  
Court Records ◽  
Seminal Work

McIntyre, in his seminal work on Scottish franchise courts, argues that these courts were in decline in this period, and of little relevance to their local population. 1 But was that really the case? This paper explores that question, using a particularly rich set of local court records. By analysing the functions and significance of one particular court it assesses the role of this one court within its local area, and considers whether it really was in decline at this time, or if it continued to perform a vital role in its local community. The period studied is the mid to late seventeenth century, a period of considerable upheaval in Scottish life, that has attracted considerable attention from scholars, though often less on the experiences of local communities and people.

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