scholarly journals Cineole, Thymol and Camphor Nasal Challenges and their Effect on Nasal Symptoms and Cough in an Animal Model

2013 ◽  
Vol 13 (2) ◽  
pp. 5-13 ◽  
Author(s):  
S Gavliakova ◽  
T Dolak ◽  
H Licha ◽  
S Krizova ◽  
J Plevkova
Keyword(s):  
Animal Model ◽  
Citric Acid ◽  
Statistical Significance ◽  
Intraperitoneal Administration ◽  
Sensory Nerves ◽  
Skin Tests ◽  
Cough Reflex ◽  
Nasal Symptoms ◽  
Nasal Application ◽  
Pre Treatment

Abstract 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.

Capsazepine inhibits cough induced by capsaicin and citric acid but not by hypertonic saline in guinea pigs

1995 ◽  
Vol 79 (4) ◽  
pp. 1082-1087 ◽  
Author(s):  
U. G. Lalloo ◽  
A. J. Fox ◽  
M. G. Belvisi ◽  
K. F. Chung ◽  
P. J. Barnes
Keyword(s):  
Citric Acid ◽  
Hypertonic Saline ◽  
Guinea Pigs ◽  
Specific Inhibitor ◽  
Inhibitory Effect ◽  
Sensory Nerves ◽  
Cough Reflex ◽  
Acidic Solutions ◽  
Nasal Irritation ◽  
Cough Response

Acidic solutions mimick many of the effects of capsaicin (Cap), including pain, bronchoconstriction, cough, and sensory neuropeptide release. Evidence from the use of the Cap antagonist capsazepine suggests that in some cases protons act at the Cap receptor. In the present study, we have investigated whether cough evoked by Cap and citric acid (CA) is mediated specifically via the Cap receptor on airway sensory nerves. We have examined the effects of capsazepine on Cap-, CA-, and hypertonic saline-induced cough and also on CA-induced nasal irritation in awake guinea pigs. Capsazepine was nebulized for 5 min before cough challenges with Cap for 5 min and CA for 10 min. Control animals were pretreated with vehicle alone. Capsazepine (100 microM) inhibited the cough response to 30 microM Cap from 0.77 +/- 0.14 coughs/min in control animals to 0.23 +/- 0.08 coughs/min (P < 0.05) and to 80 microM Cap from 1.4 +/- 0.23 to 0.3 +/- 0.11 coughs/min (P < 0.01). There was no effect, however, of lower concentrations of capsazepine (5 and 10 microM) against Cap-evoked cough. At a concentration of 100 microM, capsazepine also inhibited the coughing induced by 0.25 M CA from 1.8 +/- 0.26 to 0.93 +/- 0.31 coughs/min (P < 0.05) but not that induced by 0.5 M CA. Nasal irritation induced by 0.25 M CA, but not by 0.5 M CA, was also inhibited by capsazepine from 2.47 +/- 0.37 to 0.75 +/- 0.31 nose wipes/min (P < 0.05). This inhibitory effect of capsazepine did not appear to reflect a nonspecific suppression of the cough reflex, since cough evoked by exposure to hypertonic (7%) saline for 10 min was unaffected by pretreatment with capsazepine (100 microM). These data show that capsazepine is a specific inhibitor of Cap- and CA-induced cough in guinea pigs. Moreover, they suggest that low pH stimuli evoke cough and nasal irritation by an action at the Cap receptor, either directly or through the release of an intermediate agent.

Membrane-associated microtubular areays induced in proximal myelinated processes of dorsal root ganglia by large doses of vitamin B6

1986 ◽  
Vol 44 ◽  
pp. 368-369
Author(s):  
V.J. Montpetit ◽  
S. Dancea ◽  
L. Tryphonas ◽  
D.F. Clapin
Keyword(s):  
Animal Model ◽  
Endoplasmic Reticulum ◽  
Dorsal Root Ganglia ◽  
Rough Endoplasmic Reticulum ◽  
Dorsal Root ◽  
Vitamin B6 ◽  
Morphological Changes ◽  
Model System ◽  
Sensory Nerves ◽  
Peripheral Sensory

Very large doses of pyridoxine (vitamin B6) are neurotoxic in humans, selectively affecting the peripheral sensory nerves. We have undertaken a study of the morphological and biochemical aspects of pyridoxine neurotoxicity in an animal model system. Early morphological changes in dorsal root ganglia (DRG) associated with pyridoxine megadoses include proliferation of neurofilaments, ribosomes, rough endoplasmic reticulum, and Golgi complexes. We present in this report evidence of the formation of unique aggregates of microtubules and membranes in the proximal processes of DRG which are induced by high levels of pyridoxine.

Evaluation of Inflammatory Response of EDTA, EDTA-T, and Citric Acid in Animal Model

2010 ◽  
Vol 36 (3) ◽  
pp. 515-519 ◽  
Author(s):  
Míriam F. Zaccaro Scelza ◽  
Viviane Santos da Silva Pierro ◽  
Mauricio Alves Chagas ◽  
Licinio Esmeraldo da Silva ◽  
Pantaleo Scelza
Keyword(s):  
Animal Model ◽  
Citric Acid ◽  
Inflammatory Response

scholarly journals A combined prosodic and linguistic treatment approach for language-communication skills in children with autism spectrum disorders: A proof-of-concept study

2016 ◽  
Vol 6 (1) ◽  
pp. 8
Author(s):  
Silva Kuschke ◽  
Bart Vinck ◽  
Salomé Geertsema
Keyword(s):  
Social Interaction ◽  
Statistical Significance ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Listening Skills ◽  
Language Therapy ◽  
Baseline Design ◽  
Traditional Language ◽  
Pragmatic Skills ◽  
Pre Treatment

<p>This study aimed to determine whether the use of prosodically varied speech within a traditional language therapy framework had any effect on the listening skills, pragmatic skills and social interaction behaviour of three children with autism spectrum disorder (ASD). A single participant multiple baseline design across behaviours was implemented. Three participants with ASD were selected for this research. The listening skills, pragmatic skills and social interaction behaviour of the participants were compared before treatment, after a 3-week <br />period of treatment and after a 2-week withdrawal period from treatment, utilising prosodically varied speech within a traditional language therapy approach. Statistical significance was not calculated for each individual due to the limited data, but visual inspection indicated that all the participants showed positive behavioural changes in performance across all areas after 3 weeks of treatment, independent of their pre-treatment performance level. The use of <br />prosodically varied speech within a traditional language therapy framework appears to be a viable form of treatment for children with ASD.</p>

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 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.

433 Insomnia and Restless Legs Syndrome in Patients with Upper Airway Stimulation Therapy

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A171-A172
Author(s):  
Mohammed Jomha ◽  
Shalini Manchanda ◽  
Stephanie Stahl ◽  
Noah Parker
Keyword(s):  
Restless Legs Syndrome ◽  
Statistical Significance ◽  
Upper Airway ◽  
Post Treatment ◽  
Apnea Hypopnea Index ◽  
Upper Airway Stimulation ◽  
Therapy Adherence ◽  
Restless Legs ◽  
Obstructive Sleep ◽  
Pre Treatment

Abstract Introduction Insomnia and restless legs syndrome (RLS) are common sleep disorders that may impact obstructive sleep apnea (OSA) treatment. To our knowledge, no studies have investigated whether these comorbidities affect upper airway stimulation (UAS) therapy adherence and outcomes. This study aims to explore possible effects of insomnia and RLS in patients using UAS therapy. Methods All patients who underwent UAS system implantation for treatment of OSA at our facility were retrospectively studied. Pre- and post-implant histories and data, including diagnostic sleep testing, otolaryngology evaluation, activation results, and treatment evaluation, were analyzed. Patients with no insomnia or RLS were compared to patients with insomnia, RLS, or both. Apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), and adherence were compared pre- and post-treatment for each group. Results Sixty-four patients who have undergone UAS implantation at our center have completed post-treatment in-lab titration and evaluation of their UAS system. Insomnia was present in 47%, RLS in 28%, and both insomnia and RLS in 14%. In all groups, the overall AHI during in-lab titration was &gt;50% lower than the pre-treatment AHI (16.1+/-14.3/h vs 32.5+/-13.1/h, p&lt;0.001). While the trend in AHI reductions suggested a lower AHI in those without insomnia or RLS, the reduction did not reach statistical significance (no insomnia or RLS 15.7+/-12.9/h, insomnia 16.9+/-16.7/h, RLS 19.0+/-15.5/h, both insomnia and RLS 23.4+/-18.4/h). UAS therapy usage was reduced in patients with RLS (3.9+/-2.6 h/night, p=0.029) and in patients with both insomnia and RLS (3.9+/-1.3 h/night, p=0.046) compared to patients with neither comorbidity (5.9+/-1.9 h/night). Mean reduction in ESS was similar across groups, averaging from 11+/-5 pre-treatment to 7+/-5 post-treatment (p&lt;0.001). Conclusion Insomnia and RLS are common in patients using UAS therapy for OSA. Pre- and post-treatment residual AHI and ESS significantly improved in all patient groups assessed. A decrease in UAS usage was present in patients with RLS and both RLS and insomnia. Our study suggests that identification and treatment of RLS and insomnia may play an important role for UAS therapy adherence and efficacy, thus, optimizing care. Support (if any):

The predictive role of CA 19–9 kinetics for time-to-progression (TTP) and overall survival (OS) in patients receiving palliative first-line chemotherapy for advanced pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15637-e15637
Author(s):  
M. Haas ◽  
S. Boeck ◽  
P. Stieber ◽  
R. P. Laubender ◽  
H. Buchner ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Advanced Pancreatic Cancer ◽  
Rank Test ◽  
First Line ◽  
Predictive Role ◽  
Pre Treatment ◽  
Line Chemotherapy

e15637 Background: Previous studies showed contradictory results for a predictive role of CA 19–9 kinetics during chemotherapy in patients (pts) with pancreatic cancer (PC). Methods: We performed a retrospective, multicenter study in order to evaluate the role of CA 19–9 as a biomarker for TTP and OS in PC. Main inclusion criteria: histological confirmed diagnosis of PC, treatment with first-line chemotherapy for advanced disease, pre-treatment CA 19–9 level of > 5.2 U/ml. As CA 19–9 measurements were conducted in different laboratories using different commercial assays, we defined a subgroup of pts where CA 19–9 was assessed exclusively by the Elecsys assay (Roche Diagnostics). For the analysis of CA 19–9 kinetics, at least one follow-up measurement between day 20 and 64 during first-line chemotherapy had to be available. Pts were divided into two subgroups of CA 19–9 responders and non-responders by cut-offs of a 25% and 50% decline, respectively. OS and TTP were estimated with the Kaplan-Meier-Method, differences between the subgroups were analyzed by using the log-rank test. Results: One hundred and eighty-six pts were included, 83 of them were tested with the Elecsys method. Median age was 63 years, 90 % of the pts were treated within prospective clinical trials. Median pre-treatment CA 19–9 was 1076 U/ml (range 5.7–100,000 U/ml), the median bilirubin was 0.6 mg/dl. Median OS and TTP were 9.8 months (mo) and 5.4 mo, respectively. In univariate analysis, pts with a CA 19–9 decline of at least 25% during chemotherapy lived significantly longer (11.9 mo vs. 8.2 mo, p=0.003) and had a significantly prolonged TTP (5.8 mo vs. 4.4 mo, p=0.018) than those with a lower decline or even CA 19–9 increase. Data for the Elecsys-measurements were comparable (OS: 13.4 mo vs. 8.6 mo, p=0.004; TTP: 7.0 mo vs. 2.6 mo, p=0.003). None of the analyses demanding a CA 19–9 drop of at least 50% reached the level of statistical significance. Conclusion: An early CA 19–9 decline of 25% during first-line chemotherapy may predict OS and TTP in pts with advanced PC. Innovative statistical methods are required to improve our understanding of the utility of CA 19–9 as a predictive biomarker in PC. [Table: see text]

Association between bone involvement on PET/CT and event free survival (EFS) in follicular lymphoma (FL) grade 3b.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20068-e20068
Author(s):  
Frederique St-Pierre ◽  
Stephen M Broski ◽  
Betsy LaPlant ◽  
Kay Ristow ◽  
William R. Macon ◽  
...  
Keyword(s):  
Mayo Clinic ◽  
Statistical Significance ◽  
Bone Involvement ◽  
Clinical Failure ◽  
University Of Iowa ◽  
Soft Tissue Involvement ◽  
Pet Ct ◽  
Risk Patients ◽  
Pre Treatment ◽  
The University

e20068 Background: FL grade 3B (FL3B) is an aggressive subtype of FL with a distinct morphologic, cytogenetic and immunohistochemical profile that is associated with higher mortality compared to other subtypes of FL. FL3B is a rare disease, and data regarding its prognostication beyond grading is lacking. Recent data suggests that spleen and extranodal (EN) involvement on PET/CT predict early clinical failure in FL grades 1-3A[1]. We aimed to determine the incidence of spleen and EN involvement on PET/CT in FL3B, and whether these can predict EFS. Methods: Patients with untreated FL3B diagnosed between 2003-2016, with available pre-treatment PET/CT, were identified using the Mayo Clinic Lymphoma Database and the University of Iowa/Mayo Clinic Lymphoma SPORE database. 27 patients were included in this analysis. All but two patients received treatment with immunochemotherapy. Associations with outcomes were assessed using EFS, defined as disease progression, relapse, transformation, or death. Results: 11/27 (40.7%) of patients had EN involvement on PET/CT. The most common EN site was bone, in 8/27 (29.5%) of patients. Soft tissue involvement was present in 4/27 (14.8%) of patients. Liver, brain, and endometrial involvement were each noted once. 11/27 (40.7%) of patients had spleen involvement on PET/CT. Presence of bone involvement as detected on PET/CT was associated with lower EFS (p = 0.02). EN involvement was associated with a trend toward a lower EFS but statistical significance was not reached likely secondary to low numbers in this cohort. Results in the table are compared to results obtained from our analysis in patients with FL grade 1-3A[1]. Conclusions: Bone involvement on pre-treatment PET/CT in FL3B was associated with early clinical failure in this small cohort of 27 patients. EN involvement at diagnosis may also be associated with poorer outcomes. These findings are similar to our analysis of a large (n = 613) cohort of patients with FL grade 1-3A. These findings may aid in the prognostication of patients with newly diagnosed FL3B, to guide therapy in select higher risk patients. [Table: see text]

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