scholarly journals Prostaglandin E2 sensitizes the cough reflex centrally via EP3 receptor-dependent activation of NaV 1.8 channels

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Al-Shaimaa A. Al-Kandery ◽  
Muddanna S. Rao ◽  
Ahmed Z. El-Hashim
Keyword(s):  
Citric Acid ◽  
Nucleus Tractus Solitarius ◽  
Whole Body ◽  
Prostaglandin E ◽  
Cough Reflex ◽  
Trpv1 Antagonist ◽  
Underlying Mechanisms ◽  
Set Up ◽  
Guinea Pig Model ◽  
Ep3 Receptor

Abstract Background Cough hypersensitivity is a major characteristic feature associated with several types of cough, including chronic cough, but its underlying mechanisms remain to be fully understood. Inflammatory mediators, such as prostaglandin E2 (PGE2), have been implicated in both peripheral induction and sensitization of the cough reflex. In this study, using a conscious guinea pig model of cough, we investigated whether PGE2 can sensitize the cough reflex via central actions and, if so, via which mechanisms. Methods All drugs were administered by intracerebroventricular (i.c.v.) route and whole-body plethysmograph set-up was used for both induction, using aerosolized citric acid (0.2 M), and recording of cough. Immunohistochemistry was performed to confirm the expression of NaV 1.8 channels in the nucleus tractus solitarius (nTS). Results We show that both PGE2 and the non-selective EP1/EP3 agonist, sulprostone, dose-dependently enhanced the citric acid-induced cough (P ≤ 0.001, P ≤ 0.01, respectively). Pretreatment with the EP1 antagonist, ONO-8130, did not affect the sulprostone-induced cough sensitization, whilst the EP3 antagonist, L-798,106, dose-dependently inhibited this effect (P ≤ 0.05). Furthermore, treatment with either the EP2 agonist, butaprost or the EP4 agonist, L-902,688, had no effect on cough sensitization. Additionally, pretreatment with either the TRPV1 antagonist, JNJ-17203212 or the TRPA1 antagonist, HC-030031, alone or in combination, nor with the NaV 1.1, 1.2, 1.3, 1.4, 1.6 and 1.7 channel blocker, tetrodotoxin, had any effect on the cough. In contrast, pretreatment with the NaV 1.8 antagonist, A-803467, dose-dependently inhibited this effect (P ≤ 0.05). Furthermore, NaV 1.8 channels were shown to be expressed in the nTS. Conclusion Collectively, our findings show that PGE2 sensitizes the cough reflex centrally via EP3 receptor-dependent activation of NaV 1.8 but independently of TRPV1,TRPA1 and TTX-sensitive sodium channel activation. These results indicate that PGE2 plays an important role in central sensitization of the cough reflex and suggest that central EP3 receptors and/or NaVv 1.8 channels may represent novel antitussive molecular targets. Graphical Abstract

scholarly journals “Prostaglandin E2 Sensitizes the Cough Reflex Centrally via EP3 Receptor-dependent Activation of NaV 1.8 Channels”

2021 ◽  
Author(s):  
Al-Shaimaa Al-Kandery ◽  
Muddana Rao ◽  
Ahmed EL-Hashim
Keyword(s):  
Citric Acid ◽  
Nucleus Tractus Solitarius ◽  
Whole Body ◽  
Prostaglandin E ◽  
Cough Reflex ◽  
Trpv1 Antagonist ◽  
Underlying Mechanisms ◽  
Set Up ◽  
Guinea Pig Model ◽  
Ep3 Receptor

Abstract Background Cough hypersensitivity is a major characteristic feature associated with several types of cough, including chronic cough, but its underlying mechanisms remain to be fully understood. Inflammatory mediators, such as prostaglandin E2 (PGE2), have been implicated in peripheral induction/sensitization of the cough reflex. In this study, using a conscious guinea pig model of cough, we investigated whether PGE2 can sensitize the cough reflex via central actions and, if so, via which mechanisms. Methods All drugs were administered by intracerebroventricular (i.c.v.) route and whole-body plethysmograph set-up was used for both induction, using aerosolized citric acid (0.2 M), and recording of cough. Immunohistochemistry was performed to confirm the expression of NaV 1.8 channels in the nucleus tractus solitarius (nTS). Results We show that both PGE2 and the non-selective EP1/EP3 agonist, sulprostone, dose-dependently enhanced the citric acid-induced cough (P ≤ 0.001, P ≤ 0.01, respectively). Pretreatment with the EP1 antagonist, ONO-8130, did not affect the sulprostone-induced cough sensitization, whilst the EP3 antagonist, L-798,106, dose-dependently inhibited this effect (P ≤ 0.05). Furthermore, treatment with either the EP2 agonist, butaprost or the EP4 agonist, L-902,688, had no effect on cough sensitization. Additionally, pretreatment with either the TRPV1 antagonist, JNJ-17203212 or the TRPA1 antagonist, HC-030031, alone or in combination, nor with the NaV 1.1, 1.2, 1.3, 1.4, 1.6 and 1.7 channel blocker, tetrodotoxin, had any effect on the cough. In contrast, pretreatment with the NaV 1.8 antagonist, A-803467, dose-dependently inhibited this effect (P ≤ 0.05). Furthermore, NaV 1.8 channels were shown to be expressed in the nTS. Conclusion Collectively, our findings show that PGE2 sensitizes the cough reflex centrally via EP3 receptor-dependent activation of NaV 1.8 but independently of TRPV1/TRPA1 and TTX-sensitive sodium channel activation. These results indicate that PGE2 plays an important role in central sensitization of the cough reflex and suggest that central EP3 receptors and/or Nav 1.8 channels may represent novel antitussive molecular targets.

scholarly journals Using a simple rope-pulley system that mechanically couples the arms, legs, and treadmill reduces the metabolic cost of walking

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Daisey Vega ◽  
Christopher J. Arellano
Keyword(s):  
Metabolic Cost ◽  
Metabolic Energy ◽  
Metabolic Effects ◽  
Whole Body ◽  
Walking Ability ◽  
Arm Swing ◽  
Pulley System ◽  
Young Subjects ◽  
Walking Recovery ◽  
Set Up

Abstract Background Emphasizing the active use of the arms and coordinating them with the stepping motion of the legs may promote walking recovery in patients with impaired lower limb function. Yet, most approaches use seated devices to allow coupled arm and leg movements. To provide an option during treadmill walking, we designed a rope-pulley system that physically links the arms and legs. This arm-leg pulley system was grounded to the floor and made of commercially available slotted square tubing, solid strut channels, and low-friction pulleys that allowed us to use a rope to connect the subject’s wrist to the ipsilateral foot. This set-up was based on our idea that during walking the arm could generate an assistive force during arm swing retraction and, therefore, aid in leg swing. Methods To test this idea, we compared the mechanical, muscular, and metabolic effects between normal walking and walking with the arm-leg pulley system. We measured rope and ground reaction forces, electromyographic signals of key arm and leg muscles, and rates of metabolic energy consumption while healthy, young subjects walked at 1.25 m/s on a dual-belt instrumented treadmill (n = 8). Results With our arm-leg pulley system, we found that an assistive force could be generated, reaching peak values of 7% body weight on average. Contrary to our expectation, the force mainly coincided with the propulsive phase of walking and not leg swing. Our findings suggest that subjects actively used their arms to harness the energy from the moving treadmill belt, which helped to propel the whole body via the arm-leg rope linkage. This effectively decreased the muscular and mechanical demands placed on the legs, reducing the propulsive impulse by 43% (p < 0.001), which led to a 17% net reduction in the metabolic power required for walking (p = 0.001). Conclusions These findings provide the biomechanical and energetic basis for how we might reimagine the use of the arms in gait rehabilitation, opening the opportunity to explore if such a method could help patients regain their walking ability. Trial registration: Study registered on 09/29/2018 in ClinicalTrials.gov (ID—NCT03689647).

scholarly journals Simple low dose radiography allows precise lung volume assessment in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Amara Khan ◽  
Andrea Markus ◽  
Thomas Rittmann ◽  
Jonas Albers ◽  
Frauke Alves ◽  
...  
Keyword(s):  
Lung Function ◽  
Whole Body ◽  
Acquisition Time ◽  
Micro Ct ◽  
Lung Volumes ◽  
X Ray ◽  
Promising Tool ◽  
Volume Assessment ◽  
Set Up ◽  
Time Required

AbstractX-ray based lung function (XLF) as a planar method uses dramatically less X-ray dose than computed tomography (CT) but so far lacked the ability to relate its parameters to pulmonary air volume. The purpose of this study was to calibrate the functional constituents of XLF that are biomedically decipherable and directly comparable to that of micro-CT and whole-body plethysmography (WBP). Here, we developed a unique set-up for simultaneous assessment of lung function and volume using XLF, micro-CT and WBP on healthy mice. Our results reveal a strong correlation of lung volumes obtained from radiographic XLF and micro-CT and demonstrate that XLF is superior to WBP in sensitivity and precision to assess lung volumes. Importantly, XLF measurement uses only a fraction of the radiation dose and acquisition time required for CT. Therefore, the redefined XLF approach is a promising tool for preclinical longitudinal studies with a substantial potential of clinical translation.

scholarly journals Combined Effects of Citric Acid and Phytase Supplementation on Growth Performance, Nutrient Digestibility and Body Composition of Labeo rohita Fingerlings

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Maryam Iqbal ◽  
Muhammad Afzal ◽  
Atif Yaqub ◽  
Khalid Mahmood Anjum ◽  
Komal Tayyab
Keyword(s):  
Body Composition ◽  
Citric Acid ◽  
Growth Performance ◽  
Labeo Rohita ◽  
Antinutritional Factors ◽  
Nutrient Digestibility ◽  
Whole Body ◽  
Canola Meal ◽  
Feed Conversion ◽  
Plant Materials

Aquaculturists have been concentrating their efforts to design aquafeeds using agro by-products to reduce feed costs. However, the presence of a wide variety of antinutritional factors (ANFs) in plant materials is one of the major obstacles. For this purpose, a 2x2 factorial experiment was established to evaluate the suitability of canola meal with citric acid (CA) and phytase (PHY) supplementation for growth performance, nutrient digestibility and body composition of Labeo rohita fingerlings. Five isocaloric and isonitrogenous diets; D1 (control; without CA and PHY), D2 (CA 15 g/kg+PHY 1000 FTU/kg), D3 (CA 30 g/kg+PHY 1000 FTU/kg), D4 (CA 15 g/kg+PHY 2000 FTU/kg) and D5 (CA 30 g/kg+PHY 2000 FTU/kg) were fed to fish (mean initial weight 7.61±0.31 g) in triplicates for 90-days. The growth performance was significantly increased while feed conversion ratio was decreased with D3 compared to control and other CA and PHY supplemented groups (P<0.05). Furthermore, higher digestibility (%) of nutrients (dry matter, crude protein and ash) and improved whole-body composition was also exhibited by fish fed with D3 (P<0.05). Hence, the above results elucidate that supplementation of 30 g/kg CA with 1000 FTU/kg PHY could be a useful approach for improved growth performance, nutrients digestibility and body composition of L. rohita.

scholarly journals Immune-Mediated Mechanisms in Cofactor-Dependent Food Allergy and Anaphylaxis: Effect of Cofactors in Basophils and Mast Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Rosa Muñoz-Cano ◽  
Clara San Bartolome ◽  
Rocío Casas-Saucedo ◽  
Giovanna Araujo ◽  
Sonia Gelis ◽  
...  
Keyword(s):  
Mast Cells ◽  
Prostaglandin E ◽  
Allergic Reactions ◽  
Limited Evidence ◽  
Plasma Osmolarity ◽  
Extracellular Adenosine ◽  
Immune Mediated ◽  
Eicosanoid Metabolism ◽  
Underlying Mechanisms ◽  
Food Anaphylaxis

Cofactors may explain why in some cases food ingestion leads to anaphylaxis while in others elicits a milder reaction or tolerance. With cofactors, reactions become more severe and/or have a lower allergen threshold. Cofactors are present in up to 58% of food anaphylaxis (FAn). Exercise, NSAIDs, and alcohol are the most frequently described, although the underlying mechanisms are poorly known. Several hypotheses have suggested the influence of these cofactors on basophils and mast cells (MCs). Exercise has been suggested to enhance MC activation by increasing plasma osmolarity, redistributing blood flow, and activating adenosine and eicosanoid metabolism. NSAIDs’ cofactor effect has been related with cyclooxygenase inhibition and therefore, prostaglandin E2 (PGE2) production. Indeed, overexpression of adenosine receptor 3 (A3) gene has been described in NSAID-dependent FAn; A3 activation potentiates FcϵRI-induced MC degranulation. Finally, alcohol has been related with an increase of histamine levels by inhibition of diamino oxidase (DAO) and also with and increase of extracellular adenosine by inhibition of its uptake. However, most of these mechanisms have limited evidence, and further studies are urgently needed. In conclusion, the study of the immune-related mechanisms involved in food allergic reactions enhanced by cofactors is of the utmost interest. This knowledge will help to design both tailored treatments and prophylactic strategies that, nowadays, are non-existent.

scholarly journals Opposing effects of bronchopulmonary C-fiber subtypes on cough in guinea pigs

2018 ◽  
Vol 314 (3) ◽  
pp. R489-R498 ◽  
Author(s):  
Yang-Ling Chou ◽  
Nanako Mori ◽  
Brendan J. Canning
Keyword(s):  
Citric Acid ◽  
Guinea Pigs ◽  
Respiratory Pattern ◽  
Tracheal Mucosa ◽  
Cough Reflex ◽  
C Fibers ◽  
Selective Agonist ◽  
Nodose Ganglia ◽  
C Fiber ◽  
Opposing Effects

We have addressed the hypothesis that the opposing effects of bronchopulmonary C-fiber activation on cough are attributable to the activation of C-fiber subtypes. Coughing was evoked in anesthetized guinea pigs by citric acid (0.001–2 M) applied topically in 100-µl aliquots to the tracheal mucosa. In control preparations, citric acid evoked 10 ± 1 coughs cumulatively. Selective activation of the pulmonary C fibers arising from the nodose ganglia with either aerosols or continuous intravenous infusion of adenosine or the 5-HT3 receptor-selective agonist 2-methyl-5-HT nearly abolished coughing evoked subsequently by topical citric acid challenge. Delivering adenosine or 2-methyl-5-HT directly to the tracheal mucosa (where few if any nodose C fibers terminate) was without effect on citric acid-evoked cough. These actions of pulmonary administration of adenosine and 2-methyl-5-HT were accompanied by an increase in respiratory rate, but it is unlikely that the change in respiratory pattern caused the decrease in coughing, as the rapidly adapting receptor stimulant histamine also produced a marked tachypnea but was without effect on cough. In awake guinea pigs, adenosine failed to evoke coughing but reduced coughing induced by the nonselective C-fiber stimulant capsaicin. We conclude that bronchopulmonary C-fiber subtypes in guinea pigs have opposing effects on cough, with airway C fibers arising from the jugular ganglia initiating and/or sensitizing the cough reflex and the intrapulmonary C fibers arising from the nodose ganglia actively inhibiting cough upon activation.

scholarly journals TISSUE-SPECIFIC GLUCOSE 6-PHOSPHATE DEHYDROGENASES IN ANOPHELINE MOSQUITOES

1974 ◽  
Vol 22 (4) ◽  
pp. 260-265 ◽  
Author(s):  
UMBERTO BIANCHI ◽  
ANTONIETTINA RINALDI
Keyword(s):  
Whole Body ◽  
Mendelian Segregation ◽  
Electrophoretic Variants ◽  
Tissue Specific ◽  
Anopheles Atroparvus ◽  
Catalytically Active ◽  
Pair Mating ◽  
Set Up ◽  
Glucose 6 Phosphate Dehydrogenase

Glucose 6-phosphate dehydrogenase (G6PD) electrophoretic variants have been detected in single adult homogenates by screening laboratory strains of Anopheles atroparvus, Anopheles labranchiae and Anopheles stephensi. Pair mating crosses of A. atroparvus individuals set up to study the inheritance mechanism of this apparent polymorphism failed to show Mendelian segregation. Furthermore, monomorphic and tissue-specific G6PD bands were obtained from single adult "midgut" and single adult "skin" homogenates and the apparent polymorphism disappeared. However, the electrophoretic heterogeneity reappeared when 10 µl of the gut homogenate were added to an equal volume of the skin homogenate and permitted to interact in vitro at room temperature (20-25°C) for 4-5 min. Bovine trypsin greatly modified the anodical mobility of the skin isoenzyme. Single whole homogenates, prepared in buffers containing soybean (trypsin inhibitor), partially retained the electrophoretic heterogeneity. On this experimental background it is possible to draw the following conclusions: (a) at least two monomorphic and tissue-specific (gut and skin) G6PD isoenzymes are present in the anopheline species studied by us; (b) a factor (or factors) possessing a trypsin-like action seems to be present in the whole body homogenate, this factor seems to be particularly active in interacting with the skin enzyme; and (c) the occurrence of a similar interaction could facilitate the formation of G6PD catalytically active molecular artifacts. These data and analogous results obtained by other authors permitted us to conclude that if genetic analysis has not been performed it is very hazardous to interpret zymograms simply by assuming that any electrophoretic heterogeneity necessarily represents a genetic polymorphism.

370 The role of the prostaglandin E type 3 (EP3) receptor in modulating muscarinic induced contractions

2014 ◽  
Vol 13 (1) ◽  
pp. e370
Author(s):  
R. Hohnen ◽  
C. Meriaux ◽  
F. Raven ◽  
G.A. Van Koeveringe
Keyword(s):  
Prostaglandin E ◽  
Ep3 Receptor ◽  
Type 3

scholarly journals Biomechanical evaluation of SACH and uniaxial feet

1984 ◽  
Vol 8 (3) ◽  
pp. 147-154 ◽  
Author(s):  
J. C. H. Goh ◽  
S. E. Solomonidis ◽  
W. D. Spence ◽  
J. P. Paul
Keyword(s):  
Evaluation Method ◽  
Three Dimensional ◽  
Subjective Assessment ◽  
The United States ◽  
Whole Body ◽  
Assessment Procedure ◽  
Clear Trend ◽  
Gait Kinematics ◽  
Biomechanical Evaluation ◽  
Set Up

A review of prosthetic prescription practice reveals that in the United Kingdom about 85% of below and above-knee amputees are fitted with uniaxial feet, whereas in the United States about 80% are fitted with SACH feet. An evaluation method was developed to assess the performance of these two different types of feet. This included a subjective assessment procedure and a biomechanical evaluation of the function of the two feet and their effects on whole body gait kinematics and lower limb kinetics. Data were acquired by three Bolex H16 cine cameras and two Kistler force plates. This set-up allowed three-dimensional analysis on the prosthetic and contralateral sides of the subject. Investigations were undertaken in which an experimental prosthesis permitted the interchange of the ankle/foot while keeping the rest of the components the same. Altogether, six below knee and five above knee amputees were tested. No clear trend for preference for either type of foot was evident from the subjective survey; in general the patients showed a preference for the foot that they were accustomed to. Kinematic and kinetic analysis showed some differences in the function between the two prosthetic feet. It is the purpose of this paper to discuss these differences and their significance.

scholarly journals Characterization of Perionyx excavatus Development and Its Head Regeneration

Biology ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 273 ◽  
Author(s):  
Yun Seon Bae ◽  
Jung Kim ◽  
Jeesoo Yi ◽  
Soon Cheol Park ◽  
Hae-Youn Lee ◽  
...  
Keyword(s):  
Model System ◽  
Whole Body ◽  
Body Parts ◽  
Proliferating Cells ◽  
Perionyx Excavatus ◽  
Cns Regeneration ◽  
The Central Nervous System ◽  
Set Up ◽  
Head Regeneration

Regeneration is a biological process restoring lost or amputated body parts. The capability of regeneration varies among organisms and the regeneration of the central nervous system (CNS) is limited to specific animals, including the earthworm Perionyx excavatus. Thus, it is crucial to establish P. excavatus as a model system to investigate mechanisms of CNS regeneration. Here, we set up a culture system to sustain the life cycle of P. excavatus and characterize the development of P. excavatus, from embryo to juvenile, based on its morphology, myogenesis and neurogenesis. During development, embryos have EdU-positive proliferating cells throughout the whole body, whereas juveniles maintain proliferating cells exclusively in the head and tail regions, not in the trunk region. Interestingly, juveniles amputated at the trunk, which lacks proliferating cells, are able to regenerate the entire head. In this process, a group of cells, which are fully differentiated, reactivates cell proliferation. Our data suggest that P. excavatus is a model system to study CNS regeneration, which is dependent on the dedifferentiation of cells.

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