The effect of levocabastine and furosemide pretreatment on hyperreactive response after nasal provocation with hypotonic aerosol in subjects with allergic rhinitis.

PubMed

Anzic, Srdjan Ante; Dzepina, Davor; Kalogjera, Livije

2007-11-01

Patients with allergic rhinitis demonstrate hyperreactive response in distilled water nasal provocation, shown by significant increase in nasal airway resistance (NAR). Antihistamines, including topical antihistamine, levocabastine, reduce response in non-specific nasal provocation tests. Furosemide is a diuretic which reduces hyperreactivity in lower airways, but the mode of its action is not yet fully understood. In this study, we hypothesized that either levocabastine or furosemide pre-treatment in allergic rhinitis patients reduced response to nasal challenge with non-isotonic aerosol. To test the hypothesis, we measured the effect of pre-treatment with levocabastine and furosemide in topical application on suppression of hyperreactive response to distilled water nasal inhalation. Nasal resistance was measured, prior to and after the provocation, by active anterior rhinomanometry in two randomized groups of patients, according to pre-treatment, either by levocabastine or furosemide, 20 patients in each group, respectively. Nasal airflow resistance and level of hyperreactive response considering nasal eosinophilia were tested. Significant increase in nasal resistance following provocation was found at baseline conditions (without pre-medication); pre-treatment with levocabastine and furosemide has suppressed such response. Patients with positive nasal eosinophilia showed a significantly higher increase in nasal resistance compared to those with negative smears. Furosemide has shown significantly better protective effect on nasal resistance increase in patients with positive eosinophils nasal smears. Levocabastine and furosemide pre-treatment suppress hyperreactive response to distilled water nasal provocation. Comparison of resistances (pre-treatment vs. without) showed more protective effect of furosemide, measured on both better and worse patent side of nose, in contrast to levocabastine group for which it was shown only on better patent side prior to provocation. Protection of furosemide was significantly more pronounced in patients with significant nasal eosinophilia.

Provocation testing to assist craniomandibular pain diagnosis.

PubMed

DuPont, John S; Brown, Christopher E

2010-04-01

Patients with TMD often present with complex pain symptoms, which can make it difficult to reach a diagnosis. Usually palpation of the masticatory muscles and TM joints, range of motion testing and imaging are used in the diagnostic process. Sometimes it is necessary to evaluate the jaw moving muscles from a functional prospective because they cannot be palpated due to inaccessibility or because they have other structures that are more superficial to them. In these instances, provocation testing can be a helpful adjunct in providing some insight into what is occurring in the area being tested and localizing a suspected source of pain. Anesthesia blocking can be used to confirm any positive findings. This article explores several provocation tests that can be used to evaluate conditions of the masticatory musculature, the TM joints and the stylomandibular ligament.

Statistical prediction of space motion sickness

NASA Technical Reports Server (NTRS)

Reschke, Millard F.

1990-01-01

Studies designed to empirically examine the etiology of motion sickness to develop a foundation for enhancing its prediction are discussed. Topics addressed include early attempts to predict space motion sickness, multiple test data base that uses provocative and vestibular function tests, and data base subjects; reliability of provocative tests of motion sickness susceptibility; prediction of space motion sickness using linear discriminate analysis; and prediction of space motion sickness susceptibility using the logistic model.

Can conjunctival provocation test facilitate the diagnosis of food allergy in children?

PubMed

Krane Kvenshagen, B; Jacobsen, M; Halvorsen, R

2010-01-01

Food allergy is common in children, occurring in 5-7.5%. The diagnosis may, however, be difficult. Elevated IgE or positive skin prick test to a food allergen is often considered proof of allergy, but may represent sensitisation without clinical manifestations. For a precise diagnosis oral challenge is necessary, but this is often not performed because of risk of serious allergic reactions. The aim of this study was to evaluate whether conjunctival provocation test would facilitate the diagnosis of IgE-mediated food allergy. One hundred and forty-nine children with 174 possible diagnoses of food allergy were included. General examination, skin prick test and specific IgE were performed, as well as conjunctival provocation test of the suspected food allergen. Open food challenges and double-blind placebo controlled tests were performed in order to diagnose possible food allergy. Forty-six children with strongly positive conjunctival reactions (rubor, itching, oedema) to fifty food allergens were all proven to have allergy to the food in question. The children with negative conjunctival provocation tests showed no allergic reactions when challenged. We find that a strongly positive conjunctival reaction to a food allergen correlates well with true allergy. An oral challenge should be carefully performed. With a negative conjunctival test an oral challenge may safely be performed. Copyright © 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

Influence of body mass index on the growth hormone response to provocative testing in short children without growth hormone deficiency.

PubMed

Lee, Jieun; Yoon, Juyoung; Kang, Min Jae; Lee, Young Ah; Lee, Seong Yong; Shin, Choong Ho; Yang, Sei Won

2013-09-01

Obesity and its related factors are known to suppress the secretion of growth hormone (GH). We aimed to evaluate the influence of body mass index (BMI) on the peak GH response to provocative testing in short children without GH deficiency. We conducted a retrospective review of medical records of 88 children (2-15 yr old) whose height was less than 3 percentile for one's age and sex, with normal results (peak GH level > 10 ng/mL) of GH provocative testing with clonidine and dopamine. Peak stimulated GH level, height, weight, pubertal status and serum IGF-1 level were measured. Univariate analysis showed that the BMI standard deviation score (SDS) correlated negatively with the natural log (ln) of the peak stimulated GH level (ln peak GH). BMI SDS did not correlate significantly with sex, age, pubertal status, or ln IGF-1 level. BMI SDS correlated negatively with ln peak GH level induced by clonidine but not by dopamine. In stepwise multivariate regression analysis, BMI SDS was the only significant predictor of ln peak GH level in the combination of tests and the clonidine test, but not in the dopamine test. In children without GH deficiency, BMI SDS correlates negatively with the peak GH level. BMI SDS should be included in the analysis of the results of GH provocation tests, especially tests with clonidine.

The 15q13.3 deletion syndrome: Deficient α(7)-containing nicotinic acetylcholine receptor-mediated neurotransmission in the pathogenesis of neurodevelopmental disorders.

PubMed

Deutsch, Stephen I; Burket, Jessica A; Benson, Andrew D; Urbano, Maria R

2016-01-04

Array comparative genomic hybridization (array CGH) has led to the identification of microdeletions of the proximal region of chromosome 15q between breakpoints (BP) 3 or BP4 and BP5 encompassing CHRNA7, the gene encoding the α7-nicotinic acetylcholine receptor (α7nAChR) subunit. Phenotypic manifestations of persons with these microdeletions are variable and some heterozygous carriers are seemingly unaffected, consistent with their variable expressivity and incomplete penetrance. Nonetheless, the 15q13.3 deletion syndrome is associated with several neuropsychiatric disorders, including idiopathic generalized epilepsy, intellectual disability, autism spectrum disorders (ASDs) and schizophrenia. Haploinsufficient expression of CHRNA7 in this syndrome has highlighted important roles the α7nAChR plays in the developing brain and normal processes of attention, cognition, memory and behavior throughout life. Importantly, the existence of the 15q13.3 deletion syndrome contributes to an emerging literature supporting clinical trials therapeutically targeting the α7nAChR in disorders such as ASDs and schizophrenia, including the larger population of patients with no evidence of haploinsufficient expression of CHRNA7. Translational clinical trials will be facilitated by the existence of positive allosteric modulators (PAMs) of the α7nAChR that act at sites on the receptor distinct from the orthosteric site that binds acetylcholine and choline, the receptor's endogenous ligands. PAMs lack intrinsic efficacy by themselves, but act where and when the endogenous ligands are released in response to relevant social and cognitive provocations to increase the likelihood they will result in α7nAChR ion channel activation. Copyright © 2015 Elsevier Inc. All rights reserved.

Immediate hypersensitivity to iodinated contrast media: diagnostic accuracy of skin tests and intravenous provocation test with low dose.

PubMed

Sesé, L; Gaouar, H; Autegarden, J-E; Alari, A; Amsler, E; Vial-Dupuy, A; Pecquet, C; Francès, C; Soria, A

2016-03-01

The diagnosis of HSR to iodinated contrast media (ICM) is challenging based on clinical history and skin tests. This study evaluates the negative predictive value (NPV) of skin tests and intravenous provocation test (IPT) with low-dose ICM in patients with suspected immediate hypersensitivity reaction (HSR) to ICM. Thirty-seven patients with suspected immediate hypersensitivity reaction to ICM were included retrospectively. Skin tests and a single-blind placebo-controlled intravenous provocation test (IPT) with low-dose iodinated contrast media (ICM) were performed. Skin tests with ICM were positive in five cases (one skin prick test and five intradermal test). Thirty-six patients were challenged successfully by IPT, and only one patient had a positive challenge result, with a grade I reaction by the Ring and Messmer classification. Ten of 23 patients followed up by telephone were re-exposed to a negative tested ICM during radiologic examination; two experienced a grade I immediate reaction. For immediate hypersensitivity reaction to ICM, the NPV for skin tests and IPT with low dose was 80% (95% CI 44-97%). © 2016 John Wiley & Sons Ltd.

Reproducibility of manual pressure force on provocation of the sacroiliac joint.

PubMed

Levin, U; Nilsson-Wikmar, L; Stenström, C H; Lundeberg, T

1998-01-01

Previous studies of pain-provocation sacroiliac (SI) joint tests have revealed conflicting results. The aim of the present study was to evaluate the intra- and inter-test reliability of pressure force applied during distraction test, compression test and pressure on the apex sacralis. Seventeen physiotherapists (PTs), median age 43 years and median clinical experience 11 years, all experienced in musculoskeletal evaluation and therapy, participated in the study. Each PT performed each test on the same healthy volunteer for 20 s, on three separate occasions, at intervals of one week using a specially constructed examination table which registered pressure force. The PTs were capable of maintaining a relatively constant pressure force for 20 s. The intra-test reliability was acceptable even though there were individual differences on different occasions between those PTs who used the SI joint tests often and those who seldom or never used them. The inter-test reliability was insufficient. The findings indicate the advantage of registering pressure force as a complement for standardized methods for pain-provoking tests and when learning provocation tests, since individual variability was considerable.

Food hypersensitivity reactions in Soft Coated Wheaten Terriers with protein-losing enteropathy or protein-losing nephropathy or both: gastroscopic food sensitivity testing, dietary provocation, and fecal immunoglobulin E.

PubMed

Vaden, S L; Hammerberg, B; Davenport, D J; Orton, S M; Trogdon, M M; Melgarejo, L T; VanCamp, S D; Williams, D A

2000-01-01

The purpose of this study was to evaluate Soft Coated Wheaten Terriers (SCWTs) affected with protein-losing enteropathy (PLE) or protein-losing nephropathy (PLN) or both for allergy to food. We performed gastroscopic food-sensitivity testing, a provocative dietary trial, and measurement of fecal immunoglobulin E (IgE) in 6 SCWTs affected with PLE or PLN or both. Positive gastroscopic food-sensitivity test reactions were noted in 5 of 6 dogs. Positive reactions were found to milk in 4 dogs, to lamb in 2 dogs, and to wheat and chicken each in 1 dog. Adverse reactions to food (diarrhea, vomiting, or pruritus) were detected in all 6 dogs during the provocative dietary trial. Adverse reactions were found to corn in 5 dogs, to tofu in 3 dogs, to cottage cheese in 2 dogs, to milk in 2 dogs, to farina cream of wheat in 2 dogs, and to lamb in 2 dogs. Serum albumin concentrations significantly decreased and fecal alpha1-protease inhibitor concentration significantly increased 4 days after the provocative trial when compared with baseline values. Antigen-specific fecal IgE varied throughout the provocative trial, with peak levels following ingestion of test meals. We conclude that food hypersensitivities are present in SCWTs affected with the syndrome of PLE/PLN. Mild inflammatory bowel disease was already established in the 6 SCWTs of this report at the time of study, making it impossible to determine if food allergies were the cause or result of the enteric disease.

Eucapnic voluntary hyperventilation in diagnosing exercise-induced laryngeal obstructions.

PubMed

Christensen, Pernille M; Rasmussen, Niels

2013-11-01

Exercise-induced laryngeal obstructions (EILOs) cause exercise-related respiratory symptoms (ERRS) and are important differential diagnoses to exercise-induced asthma. The diagnostic method for EILOs includes provocation to induce the obstruction followed by a verification of the obstruction and the degree thereof. The objective of the present study was to examine if a eucapnic voluntary hyperventilation (EVH) test could induce laryngeal obstructions laryngoscopically identical in subtypes and development as seen during an exercise test. EVH and exercise testing with continuous laryngoscopy were performed during a screening of two national athletic teams (n = 67). The laryngoscopic recordings were examined for usability, abnormalities and maximal supraglottic and glottic obstruction using two currently available methods (Eilomea and CLE-score). The participants were asked questions on ERRS, and whether the symptoms experienced during each provocation matched those experienced during regular training. A total of 39 completed both tests. There were no significant differences in subtypes and development thereof, the experience of symptoms, and specificity and sensitivity between the methods. Significantly more recordings obtained during the exercise test were usable for evaluation primarily due to resilient mucus on the tip of the fiber-laryngoscope in the EVH test. Only recordings of six athletes from both provocation methods were usable for evaluation using the Eilomea method (high-quality demand). Amongst these, a linear correlation was found for the glottic obstruction. EVH tests can induce EILOs. However, the present test protocol needs adjustments to secure better visualisation of the larynx during provocation.

Acetylcholine test in patients with angina pectoris and normal coronary angiography

NASA Astrophysics Data System (ADS)

Barbieri, Enrico; Destro, Gianni; Oliva, Massimo; Zardini, Piero

1994-02-01

Angina pectoris with normal coronary artery on the coronary angiography is an intriguing issue. Intracoronary infusion of acetylcholine has recently been used to test the integrity of endothelial cells. We studied 16 patients with this syndrome. A relationship has been found between the acetylcholine test and the exercise stress test in normotensive patients. The presence of hypertension makes the evaluation of the test more unpredictable, probably because of the damage on the endothelial cells related to systemic hypertension.

Hip range of motion and provocative physical examination tests reliability and agreement in asymptomatic volunteers

PubMed Central

Prather, H; Harris-Hayes, M; Hunt, D; Steger-May, K; Mathew, V; Clohisy, JC

2012-01-01

Objective The objectives of this study are the following: 1) report passive hip ROM in asymptomatic young adults, 2) report the intra-tester and inter-tester reliability of hip ROM measurements among testers of multiple disciplines, 3) report the results of provocative hip tests and tester agreement. Design descriptive epidemiology study Setting tertiary university Participants Twenty-eight young adult volunteers without musculoskeletal symptoms, history of disorder or surgery involving the lumbar spine or lower extremities were enrolled and completed the study. Methods Asymptomatic young adult volunteers completed questionnaires and were examined by two blinded examiners during a single session. The testers were physical therapists and physicians. Hip range of motion and provocative tests were completed by both examiners on each hip. Main Outcome Measurements Inter and intra-rater reliability for ROM and agreement for provocative tests was determined. Results Twenty-eight asymptomatic adults with mean age 31 years old (range 18–51 years) and mean modified Harris Hip Score of 99.5 ± 1.5 and UCLA Activity score of 8.8 ± 1.2 completed the study. Intra-rater agreement was excellent for all hip range of motion measurements, with intraclass correlation coefficients (ICCs) ranging from 0.76 to 0.97 with similar agreement if the examiner was a physical therapist or a physician. Excellent inter-rater reliability was found for hip flexion ICC 0.87 (95% CI 0.78 to 0.92), supine internal rotation ICC 0.75 (95% CI 0.60 to 0.84) and prone internal rotation ICC 0.79 (95% CI 0.66 to 0.87). The least reliable measurements were supine hip abduction (ICC 0.34) and supine external rotation (ICC 0.18). Agreement between examiners ranged from 96–100% for provocative hip tests which included the hip impingement, resisted straight leg raise, FABER/Patrick’s and log roll tests. Conclusions Specific hip ROM measures show excellent inter-rater reliability and provocative hip tests show good agreement among multiple examiners and medical disciplines. Further studies are needed to assess the utilization of these measurements and tests as a part of a hip screening examination to assess for young adults at risk intra-articular hip disorders prior to the onset of degenerative changes. PMID:20970757

Reliability and validity of three pain provocation tests used for the diagnosis of chronic proximal hamstring tendinopathy.

PubMed

Cacchio, Angelo; Borra, Fabrizio; Severini, Gabriele; Foglia, Andrea; Musarra, Frank; Taddio, Nicola; De Paulis, Fosco

2012-09-01

The clinical assessment of chronic proximal hamstring tendinopathy (PHT) in athletes is a challenge to sports medicine. To be able to compare the results of research and treatments, the methods used to diagnose and evaluate PHT must be clearly defined and reproducible. To assess the reliability and validity of three pain provocation tests used for the diagnosis of PHT. Ninety-two athletes with (N=46) and without (N=46) PHT were examined by one physician and two physiotherapists, who were trained in the examination techniques before the study. The examiners were blinded to the symptoms and identity of the athletes. The three pain provocation tests examined were the Puranen-Orava, bent-knee stretch and modified bent-knee stretch tests. Intraclass correlation coefficients (ICCs) based on the repeated measures analysis of variance were used to analyse the intraexaminer and interexaminer reliability, while sensitivity, specificity, predictive values and likelihood ratios were used to determine the validity of the three tests. The ICC values in all three tests revealed a high correlation (range 0.82 to 0.88) for the interexaminer reliability and a high-to-very high correlation (range 0.87 to 0.93) for the intraexaminer reliability. All three tests displayed a moderate-to-high validity, with the highest degree of validity being yielded by the modified bent-knee stretch test. All three pain provocation tests proved to be of potential value in assessing chronic PHT in athletes. However, we recommend that they be used in conjunction with other objective measures, such as MRI.

Muscle Weakness in the Empty and Full Can Tests Cannot Differentiate Rotator Cuff Tear from Cervical Spondylotic Amyotrophy: Pain Provocation is a Useful Finding.

PubMed

Iwata, Eiichiro; Shigematsu, Hideki; Inoue, Kazuya; Egawa, Takuya; Sakamoto, Yoshihiro; Tanaka, Yasuhito

2017-01-01

Rotator cuff tears and cervical spondylotic amyotrophy (CSA) are often confused as the main symptom in those with difficulty in shoulder elevation. Empty and full can tests are frequently used for the clinical diagnosis of rotator cuff tears. The aim of the present study was to investigate whether the empty and full can test results can help differentiate rotator cuff tears from CSA. Twenty-seven consecutive patients with rotator cuff tears and 25 with CSA were enrolled. We prospectively performed empty and full can tests in patients with rotator cuff tears and CSA. The following signs were considered positive: (a) muscle weakness during the empty can test, (b) muscle weakness during the full can test, (c) pain provocation during the empty can test, and (d) pain provocation during the full can test. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of rotator cuff tears for each positive finding. The sensitivity and specificity of each index were as follows (sensitivity, specificity, PPV, NPV): (a) 77.8%, 0%, 45.7%, 0%; (b) 66.7%, 4.0%, 42.9%, 10.0%; (c) 88.9%, 96.0%, 96.0%, 88.9%; and (d) 74.1%, 96.0%, 95.2%, 77.4%. There were significant differences for each index. Muscle weakness during the empty and full can tests was not useful in differentiating rotator cuff tears from CSA because of low specificity and PPV. However, pain provocation was useful in differentiating these two conditions because of high specificity and PPV.

Diagnostic Accuracy of the Neck Tornado Test as a New Screening Test in Cervical Radiculopathy.

PubMed

Park, Juyeon; Park, Woo Young; Hong, Seungbae; An, Jiwon; Koh, Jae Chul; Lee, Youn-Woo; Kim, Yong Chan; Choi, Jong Bum

2017-01-01

The Spurling test, although a highly specific provocative test of the cervical spine in cervical radiculopathy (CR), has low to moderate sensitivity. Thus, we introduced the neck tornado test (NTT) to examine the neck and the cervical spine in CR. The aim of this study was to introduce a new provocative test, the NTT, and compare the diagnostic accuracy with a widely accepted provocative test, the Spurling test. Retrospective study. Medical records of 135 subjects with neck pain (CR, n = 67; without CR, n = 68) who had undergone cervical spine magnetic resonance imaging and been referred to the pain clinic between September 2014 and August 2015 were reviewed. Both the Spurling test and NTT were performed in all patients by expert examiners. Sensitivity, specificity, and accuracy were compared for both the Spurling test and the NTT. The sensitivity of the Spurling test and the NTT was 55.22% and 85.07% ( P < 0.0001); specificity, 98.53% and 86.76% ( P = 0.0026); accuracy, 77.04% and 85.93% ( P = 0.0423), respectively. The NTT is more sensitive with superior diagnostic accuracy for CR diagnosed by magnetic resonance imaging than the Spurling test.

Retrospective Comparison of Cardiac Testing and Results on Inpatients with Low Pretest Probability Compared with Moderate/High Pretest Probability for Coronary Artery Disease.

PubMed

Lear, Aaron; Huber, Merritt; Canada, Amy; Robertson, Jessica; Bosman, Evan; Zyzanski, Stephen

2018-01-01

To determine whether admission, and provocative stress testing of patients who have ruled out for acute coronary syndrome put patients with low-risk category for coronary artery disease (CAD) at risk for false-positive provocative stress testing and unnecessary coronary angiogram/imaging. A retrospective chart review was performed on patients between 30 and 70 years old, with no pre-existing diagnosis of CAD, admitted to observation or inpatient status chest pain or related complaints. Included patients were categorized based on Duke Clinical Score for pretest probability for CAD into either low-risk group, or moderate/high-risk group. The inpatient course was compared including whether provocative stress testing was performed; results of stress testing; whether patients underwent further coronary imaging; and what the results of the further imaging showed. 543 patients were eligible: 305 low pretest probability, and 238 moderate/high pretest probability. No difference was found in rate of stress testing relative risk (RR) = 1.01 (95% CI, 0.852 to 1.192; P = 0); rate of positive or equivocal stress tests between the 2 groups: RR = 0.653 (95% CI, 0.415 to 1.028; P = .07,). Low-pretest-probability patients had a lower likelihood of positive coronary imaging after stress test, RR = 0.061 (95% CI, 0.004 to 0.957; P = .001). Follow-up provocative testing of all patients admitted/observed after emergency department presentation with chest pain is unlikely to find CAD in patients with low pretest probability. Testing all low-probability patients puts them at increased risk for unnecessary invasive confirmatory testing. Further prospective testing is needed to confirm these retrospective results. © Copyright 2018 by the American Board of Family Medicine.

A commercially available immunoglobulin E-based test for food allergy gives inconsistent results in healthy ponies.

PubMed

Dupont, S; De Spiegeleer, A; Liu, D J X; Lefère, L; van Doorn, D A; Hesta, M

2016-01-01

Commercial immunoglobulin E (IgE)-based tests are available for diagnosis of food allergies and are commonly used in equine practice. However, these tests have been proven unreliable as a screening method in man and other species, but not critically evaluated in equids. Therefore, a commercially available IgE-based test for horses was evaluated. To evaluate the consistency of the results obtained with a commercially available IgE-based test for food allergy diagnosis in ponies (Phase I) and to subject ponies to a provocation trial with the presumed allergens (Phase II). Allergen screening followed by experimental food provocation trials in healthy ponies. Blood samples of 17 healthy Shetland ponies were taken at 2 different time points, sent blinded to a commercial laboratory for screening of common food allergens and the results were evaluated for consistency (Phase I). Ponies that were positive for food allergens were consecutively challenged orally with each allergen separately for 14 days (Phase II). A washout period of one week was applied in ponies with multiple positive results. Clinical parameters and serum amyloid A were monitored during the provocation trial. Only 7/17 ponies were negative on the IgE-based test at the 2 time points, 3 had positive results twice but only one tested positive twice for the same food allergen. No abnormalities were noted during the provocation trials. This study demonstrated that this IgE-based test is not a reliable screening tool for food allergy in healthy equids. © 2015 EVJ Ltd.

Inhaled Mannitol as a Laryngeal and Bronchial Provocation Test.

PubMed

Tay, Tunn Ren; Hoy, Ryan; Richards, Amanda L; Paddle, Paul; Hew, Mark

2017-03-01

Timely diagnosis of vocal cord dysfunction (VCD), more recently termed "inducible laryngeal obstruction," is important because VCD is often misdiagnosed as asthma, resulting in delayed diagnosis and inappropriate treatment. Visualization of paradoxical vocal cord movement on laryngoscopy is the gold standard for diagnosis, but is limited by poor test sensitivity. Provocation tests may improve the diagnosis of VCD, but the diagnostic performance of current tests is less than ideal. Alternative provocation tests are required. This pilot study demonstrates the feasibility of using inhaled mannitol for concurrent investigation of laryngeal and bronchial hyperresponsiveness. Consecutive patients with suspected VCD seen at our institution's asthma clinic underwent flexible laryngoscopy at baseline and following mannitol challenge. VCD was diagnosed on laryngoscopy based on inspiratory adduction, or >50% expiratory adduction of the vocal cords. Bronchial hyperresponsiveness after mannitol challenge was also assessed. We evaluated the interrater agreement of postmannitol laryngoscopy between respiratory specialists and laryngologists. Fourteen patients with suspected VCD in the context of asthma evaluation were included in the study. Mannitol provocation demonstrated VCD in three of the seven patients with normal baseline laryngoscopy (42.9%). Only two patients had bronchial hyperresponsiveness. There was substantial interrater agreement between respiratory specialists and laryngologists, kappa = 0.696 (95% confidence interval: 0.324-1) (P = 0.006). Inhaled mannitol can be used to induce VCD. It is well tolerated and can evaluate laryngeal and bronchial hyperresponsiveness at the same setting. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

[Safety and efficacy of a new preservative-free levocabastine ophthalmic solution (Levofree®) using the conjunctival provocation test].

PubMed

Allaire, C; Siou-Mermet, R; Bassols, A

2012-09-01

To evaluate the safety and efficacy of preservative-free levocabastine 0.05 % ophthalmic solution compared to placebo (vehicle) and to preserved levocabastine 0.05 % ophthalmic suspension in the prevention of allergic conjunctivitis induced by a conjunctival provocation test. Ninety-two subjects (18-50 years) with a previous history of allergic conjunctivitis to pollen were randomised to receive either preservative-free levocabastine solution in one eye and preserved levocabastine suspension in the fellow eye (n=69), or preservative-free levocabastine in one eye and placebo in the fellow eye (n=23). One drop of each product was administered 10 minutes (visit 3) and 4 hours (visit 4) prior to the provocation test. The primary efficacy criterion was the sum of the itching and conjunctival hyperemia scores assessed at 3, 5 and 10 minutes after the provocation test. The safety evaluation included adverse events, visual acuity, intra-ocular pressure and study drug drop sensation. The efficacy of the preservative-free solution was significantly higher than that of placebo at all time points (P≤0.01) with one exception at visit 4 (3 minutes after the provocation test). It was significantly higher than that of the preserved suspension at visit 3, and equivalent at visit 4. The incidence of adverse events was lower with the preservative-free solution than with the preserved suspension. 94.2 % and 95.7 % subjects rated preservative-free levocabastine drop sensation as "good" or "very good" at visits 3 and 4 respectively, whereas these rates were 68.1 % and 63.8 % with preserved levocabastine. This difference between the two formulations was highly statistically significant (P<0.001). The efficacy of preservative-free levocabastine was superior to that of the placebo and of the preserved suspension at visit 3, at least as effective as the preserved suspension at visit 4, and better tolerated at each visit. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

The pleasure of revenge: retaliatory aggression arises from a neural imbalance toward reward

PubMed Central

DeWall, C. Nathan

2016-01-01

Most of daily life hums along peacefully but provocations tip the balance toward aggression. Negative feelings are often invoked to explain why people lash out after an insult. Yet people might retaliate because provocation makes aggression hedonically rewarding. To test this alternative hypothesis, 69 participants underwent functional neuroimaging while they completed a behavioral aggression task that repeatedly manipulated whether aggression was preceded by an instance of provocation or not. After provocation, greater activity in the nucleus accumbens (NAcc) (a brain region reliably associated with reward) during aggressive decisions predicted louder noise blasts administered in retaliation. Greater NAcc activation was also associated with participants’ history of real-world violence. Functional connectivity between the NAcc and a regulatory region in the lateral prefrontal cortex related to lower retaliatory aggression. These findings suggest that provocation tips the neural balance towards hedonic reward, which fosters retaliatory aggression. Although such pleasure of inflicting pain may promote retaliatory aggression, self-regulatory processes can keep such aggressive urges at bay. Implications for theory and violence reduction are discussed. PMID:26117504

Vasospastic angina and microvascular angina are differentially influenced by PON1 A632G polymorphism in the Japanese.

PubMed

Mashiba, Junko; Koike, George; Kamiunten, Hitoshi; Ikeda, Manami; Sunagawa, Kenji

2005-12-01

Ethnicity and smoking are well-known risk factors for the pathogenesis of coronary vasospasm. Oxidative stress induced by smoking plays a crucial role in coronary vasospasm, but is not enough to account for the pathogenesis of coronary vasospasm, indicating that genetic factors are strongly involved. The study group comprised 162 vasospastic angina patients (VSAs), 61 microvascular angina patients (MVAs) and 61 non-responders (NRs) diagnosed by acetylcholine provocation test. Four polymorphisms of the oxidative stress related genes, cytochrome b-245, alpha polypeptide gene (CYBA) C242T and A640G, paraoxonase 1 gene (PON1) A632G, phospholipase A2 group VII gene (PLA2G7) G994T were genotyped. Allele frequency of PON1 632-G was significantly higher in both the VSA with dominant fashion and the MVA with recessive fashion compared with NR. This association was strongly influenced by gender in the MVA only. There were no significant associations between the other polymorphisms and coronary vasospasm. In addition, the allele frequency of PON1 632-G in the Japanese was higher than in Caucasians. There was a significant association between PON1 A632G polymorphism and MVA as well as VSA, but the impact of this on VSA and MVA is different in the Japanese.

Diagnostic Accuracy of the Neck Tornado Test as a New Screening Test in Cervical Radiculopathy

PubMed Central

Park, Juyeon; Park, Woo Young; Hong, Seungbae; An, Jiwon; Koh, Jae Chul; Lee, Youn-Woo; Kim, Yong Chan; Choi, Jong Bum

2017-01-01

Background: The Spurling test, although a highly specific provocative test of the cervical spine in cervical radiculopathy (CR), has low to moderate sensitivity. Thus, we introduced the neck tornado test (NTT) to examine the neck and the cervical spine in CR. Objectives: The aim of this study was to introduce a new provocative test, the NTT, and compare the diagnostic accuracy with a widely accepted provocative test, the Spurling test. Design: Retrospective study. Methods: Medical records of 135 subjects with neck pain (CR, n = 67; without CR, n = 68) who had undergone cervical spine magnetic resonance imaging and been referred to the pain clinic between September 2014 and August 2015 were reviewed. Both the Spurling test and NTT were performed in all patients by expert examiners. Sensitivity, specificity, and accuracy were compared for both the Spurling test and the NTT. Results: The sensitivity of the Spurling test and the NTT was 55.22% and 85.07% (P < 0.0001); specificity, 98.53% and 86.76% (P = 0.0026); accuracy, 77.04% and 85.93% (P = 0.0423), respectively. Conclusions: The NTT is more sensitive with superior diagnostic accuracy for CR diagnosed by magnetic resonance imaging than the Spurling test. PMID:28824298

Comorbid Latent Adrenal Insufficiency with Autoimmune Thyroid Disease.

PubMed

Yamamoto, Toshihide

2015-09-01

Autoimmune thyroid disease (ATD) has been occasionally observed in patients with primary adrenal insufficiency (PAI). In contrast, less than 20 cases of comorbid PAI with ATD have been found in the English literature. One conceivable reason is difficulty in detecting latent PAI. Information of clinical presentation and diagnostics is sought to facilitate diagnosis of latent PAI. Latent PAI was pursued in 11 patients among 159 ATD patients. All of them were maintained in a euthyroid state. Except for one patient with nonrheumatic musculoskeletal symptoms, the other patients, who were asymptomatic in their daily lives, presented with recurrent nonspecific gastrointestinal symptoms or fatigue in stress-associated circumstances. Morning cortisol level <303 nmol/l was used as an inclusion criterion. Their basal adrenocorticotropic hormone levels were normal. The adrenal status was examined by a provocation test, either an insulin-induced hypoglycemia test or a 1-μg intravenous corticotrophin test. Eleven patients showed subnormal cortisol response. They were supplemented with hydrocortisone of doses ≤15 mg/day. After a few months of supplementation, PAI was confirmed by another provocation test. Three patients were excluded because of dissociation of two provocation tests. Comorbid latent PAI with ATD was pursued from the symptoms stated above and proven by two provocation tests; it was found in 5% (8/159) of the patients. When patients with ATD are troubled by recurrent stress-associated gastrointestinal or constitutional symptoms or nonrheumatic musculoskeletal symptoms which have remained unrelieved by adjustment of thyroid medication, these symptoms may be a manifestation of comorbid latent PAI. It is worth investigating such patients for latent PAI.

Test-retest Reliability in Reporting the Pain Induced by a Pain Provocation Test: Further Validation of a Novel Approach for Pain Drawing Acquisition and Analysis.

PubMed

Leoni, Diego; Falla, Deborah; Heitz, Carolin; Capra, Gianpiero; Clijsen, Ron; Egloff, Michele; Cescon, Corrado; Baeyens, Jean-Pierre; Barbero, Marco

2017-02-01

Pain drawings (PD) are frequently used in research to illustrate the pain response to pain provocation tests. However, there is a lack of data on the reliability in defining the extent and location of pain. We investigated the test-retest reliability in reporting an acute painful sensation induced by a pain provocation test using a novel approach for PD acquisition and analysis in healthy volunteers. Forty healthy volunteers participated. Each participant underwent 2 upper limb neurodynamic tests 1 (ULNT1), once to the point of pain onset (PO) and once until the point of submaximal pain (SP). After each ULNT1, participants completed 2 consecutive PD with an interval of 1 minute. Custom software was used to quantify the pain extent and analyze the pain overlap. The test-retest reliability of pain extent was examined using Intraclass Correlation Coefficient (ICC 2,1 ) and Bland-Altman plots. Pain location reliability was examined using the Jaccard similarity coefficient (JSC). The ICC values for PO and SP were 0.98 (95% CI: 0.96-0.99) and 0.97 (95% CI: 0.95-0.98), respectively. The mean difference and 95% limits of agreement (± 1.96 SD) in the Bland-Altman plots were 14 pixels (-1080;1110) for PO, and 145 (-1610;1900) for SP. The median JSCs (Q1;Q3) were 0.73 (0.64;0.80) for PO and 0.76 (0.65;0.79) for SP. Pain drawings is a reliable instrument to investigate pain extent and pain location in healthy individuals experiencing an acute painful sensation induced by a pain provocation test. © 2016 World Institute of Pain.

A systematic review of the diagnostic accuracy of provocative tests of the neck for diagnosing cervical radiculopathy

PubMed Central

Pool, Jan J. M.; van Tulder, Maurits W.; Riphagen, Ingrid I.; de Vet, Henrica C. W.

2006-01-01

Clinical provocative tests of the neck, which position the neck and arm inorder to aggravate or relieve arm symptoms, are commonly used in clinical practice in patients with a suspected cervical radiculopathy. Their diagnostic accuracy, however, has never been examined in a systematic review. A comprehensive search was conducted in order to identify all possible studies fulfilling the inclusion criteria. A study was included if: (1) any provocative test of the neck for diagnosing cervical radiculopathy was identified; (2) any reference standard was used; (3) sensitivity and specificity were reported or could be (re-)calculated; and, (4) the publication was a full report. Two reviewers independently selected studies, and assessed methodological quality. Only six studies met the inclusion criteria, which evaluated five provocative tests. In general, Spurling’s test demonstrated low to moderate sensitivity and high specificity, as did traction/neck distraction, and Valsalva’s maneuver. The upper limb tension test (ULTT) demonstrated high sensitivity and low specificity, while the shoulder abduction test demonstrated low to moderate sensitivity and moderate to high specificity. Common methodological flaws included lack of an optimal reference standard, disease progression bias, spectrum bias, and review bias. Limitations include few primary studies, substantial heterogeneity, and numerous methodological flaws among the studies; therefore, a meta-analysis was not conducted. This review suggests that, when consistent with the history and other physical findings, a positive Spurling’s, traction/neck distraction, and Valsalva’s might be indicative of a cervical radiculopathy, while a negative ULTT might be used to rule it out. However, the lack of evidence precludes any firm conclusions regarding their diagnostic value, especially when used in primary care. More high quality studies are necessary in order to resolve this issue. PMID:17013656

Investigation of carbachol and PACAP38 in a human model of migraine.

PubMed

Schytz, Henrik Winther

2010-12-01

The parasympathetic signalling molecules acetylcholine, pituitary adenylate cyclase activating peptide-38 (PACAP38) and vasoactive intestinal peptide (VIP) may be released from parasympathetic fibres and activate sensory nerve fibres during migraine attacks. Recently, it was shown that VIP does not induce migraine-like attacks in migraine patients. Interestingly, PACAP38 activates the same VPAC receptors as VIP, but also specifically activates the PAC1 receptor. The present thesis includes four double-blind placebo-controlled crossover studies aimed to explore the role of acetylcholine, PACAP and VIP in migraine and head pain. In study I-III we investigated acetylcholine, via the analogue carbachol, and PACAP38 in a human model of migraine. In study IV we studied if PACAP38 and VIP might induce central sensitization, neurogenic inflammation and mast cell degranulation in a cutaneous model of acute pain. Study I-II showed that carbachol induced short lasting mild headache and moderate cephalic vasodilatation in both healthy volunteers and migraine patients, but did not induce migraine-like attacks. In study III PACAP38 induced headache in healthy subjects and delayed migraine-like attacks in migraine patients as well as sustained dilatation of cephalic vessels. In study IV VIP and PACAP38 evoked skin pain, central sensitization, neurogenic inflammation and mast cell degranulation, but VIP showed to be more potent than PACAP38 in inducing neurogenic inflammation and mast cell degranulation. In conclusion, we found that carbachol infusion was not a good model for experimental migraine provocation, probably because the maximal dose was insufficient to produce enough nitric oxide to trigger migraine. PACAP38 infusion is a new pathway for migraine induction and the results from study IV suggest that neurogenic inflammation and mast cell degranulation are unlikely to cause PACAP38 induced migraine. The present thesis contributes to our knowledge on migraine pathophysiology and suggests PAC1 receptor antagonism as a new target for migraine treatment.

Examination of patients for carpal tunnel syndrome sensibility, provocative, and motor testing.

PubMed

Palumbo, Carl F; Szabo, Robert M

2002-05-01

The value of a test for carpal tunnel syndrome (CTS) depends on the purpose of performing the test. When screening a large population with a low prevalence for CTS, a test with a high sensitivity is needed so that no possible case goes undetected. However, in order to establish a diagnosis, a more specific test is required. Using a combination of physical examination techniques, including sensibility and provocative testing, the probability of correctly diagnosing CTS without relying on electrodiagnostic studies can be very high. Because CTS is a clinical syndrome, the diagnosis should be made on clinical grounds. Electrodiagnosis is extremely important, however, in its ability to objectively document median nerve slowing and eliminate other competing differential diagnoses.

Correcting for possible tissue distortion between provocation and assessment in skin testing: the divergent beam UVB photo-test.

PubMed

O'Doherty, Jim; Henricson, Joakim; Falk, Magnus; Anderson, Chris D

2013-11-01

In tissue viability imaging (TiVi), an assessment method for skin erythema, correct orientation of skin position from provocation to assessment optimizes data interpretation. Image processing algorithms could compensate for the effects of skin translation, torsion and rotation realigning assessment images to the position of the skin at provocation. A reference image of a divergent, UVB phototest was acquired, as well as test images at varying levels of translation, rotation and torsion. Using 12 skin markers, an algorithm was applied to restore the distorted test images to the reference image. The algorithm corrected torsion and rotation up to approximately 35 degrees. The radius of the erythemal reaction and average value of the input image closely matched that of the reference image's 'true value'. The image 'de-warping' procedure improves the robustness of the response image evaluation in a clinical research setting and opens the possibility of the correction of possibly flawed images performed away from the laboratory setting by the subject/patient themselves. This opportunity may increase the use of photo-testing and, by extension, other late response skin testing where the necessity of a return assessment visit is a disincentive to performance of the test. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

General anaesthetics and the acetylcholine-sensitivity of cortical neurons.

PubMed Central

Smaje, J C

1976-01-01

1The effects of general anaesthetics on neuronal responses to iontophoretically-applied acetylcholine have been examined in slices of guinea-pig olfactory cortex maintained in vitro. 2 Acetylcholine excited 61% of the prepiriform neurones tested. The excitation was blocked by atropine, but not by dihydro-beta-erythroidine or gallamine. 3 Alphaxalone reversibly depressed the acetylcholine-sensitivity of prepiriform neurones. Pentobarbitone did not consistently depress the acetylcholine sensitivity of these cells. 4 Ether, methoxyflurane, trichloroethylene and halothane caused a dose-related augmentation of acetylcholine-induced firing. 5 These results show that general anaesthetics do not necessarily depress the sensitivity of nerve cells to all excitatory substances and that different anaesthetics may affect a particular excitatory process in various ways. PMID:990586

Impulsivity and suicidality: the mediating role of painful and provocative experiences.

PubMed

Bender, Theodore W; Gordon, Kathryn H; Bresin, Konrad; Joiner, Thomas E

2011-03-01

Multiple studies have reported a link between high levels of impulsivity and suicidal behavior. Joiner's (2005) explanation for this link is that impulsive individuals have a greater tendency to experience painful and provocative events that habituate them to fear and pain, which leads to an acquired capability for engaging in suicidal behavior. Study 1 tested Joiner's (2005) hypothesis in a sample of 182 undergraduate students who completed self-report questionnaires on impulsivity, frequency of painful and provocative events, and acquired capability for suicide. In addition to self-report, pain tolerance (an aspect of acquired capability for suicide) was measured with a pressure algometer. Study 2 sought to replicate our findings from Study 1 in a sample of 516 clinical outpatients using a multi-faceted measure of impulsivity. Consistent with prediction, product of coefficients tests for mediation (MacKinnon et al., 2002) revealed that impulsivity has an indirect relationship with acquired capability for suicidal behavior, and that this relationship is mediated by painful and provocative events. Data from our studies are cross-sectional in nature, which does not allow for conclusions about the temporal ordering of our variables. In addition, self-report was used to measure most variables. Future research may benefit from a longitudinal design and the inclusion of other modes of assessment (e.g., behavioral measures of impulsivity). Our findings suggest that the link between impulsivity and suicidal behavior occurs because impulsive people tend to have a greater capability for suicidal behavior, which they have acquired through experiencing painful and provocative events. Copyright © 2010 Elsevier B.V. All rights reserved.

Testosterone reactivity to provocation mediates the effect of early intervention on aggressive behavior.

PubMed

Carré, Justin M; Iselin, Anne-Marie R; Welker, Keith M; Hariri, Ahmad R; Dodge, Kenneth A

2014-05-01

We tested the hypotheses that the Fast Track intervention program for high-risk children would reduce adult aggressive behavior and that this effect would be mediated by decreased testosterone responses to social provocation. Participants were a subsample of males from the full trial sample, who during kindergarten had been randomly assigned to the 10-year Fast Track intervention or to a control group. The Fast Track program attempted to develop children's social competencies through child social-cognitive and emotional-coping skills training, peer-relations coaching, academic tutoring, and classroom management, as well as training for parents to manage their child's behavior. At a mean age of 26 years, participants responded to laboratory provocations. Results indicated that, relative to control participants, men assigned to the intervention demonstrated reduced aggression and testosterone reactivity to social provocations. Moreover, reduced testosterone reactivity mediated the effect of intervention on aggressive behavior, which provides evidence for an enduring biological mechanism underlying the effect of early psychosocial intervention on aggressive behavior in adulthood.

Aminopenicillin-associated exanthem: lymphocyte transformation testing revisited.

PubMed

Trautmann, A; Seitz, C S; Stoevesandt, J; Kerstan, A

2014-12-01

The lymphocyte transformation test (LTT) has been promoted as in-vitro test for diagnosis of drug hypersensitivity. For determination of statistical LTT sensitivity, series of patients with clinically uniform reactions followed by complete drug hypersensitivity work-up are mandatory. Assessment of LTT specificity requires control patients who tolerated exposure to the drug studied. To prospectively determine the diagnostic value of the LTT in a clinically and diagnostically well-defined series of patients. Patients with exanthematous skin eruptions after ampicillin (AMP) intake were included in this study. After exclusion or confirmation of delayed-onset allergic AMP hypersensitivity by skin and provocation testing, two independent LTTs were performed: one standard LTT and a modified LTT with additional anti-CD3/anti-CD28 monoclonal antibody stimulation. By testing, delayed-onset allergic AMP hypersensitivity was diagnosed in 11 patients and definitely ruled out in 26. The standard LTT reached a diagnostic sensitivity of 54.5% while the modified LTT yielded 72.7%. However, the methodical test modification resulted in a decline of specificity from 92.3% (standard LTT) to 76.9%. In cases of AMP-associated exanthems, the diagnostic value of the LTT compared with routine allergy testing is limited. When evaluating such exanthems, provocation testing remains the gold standard. Delayed reading of intradermal skin tests remains most useful to avoid positive provocation reactions. © 2014 John Wiley & Sons Ltd.

Does short-term exposure to mobile phone base station signals increase symptoms in individuals who report sensitivity to electromagnetic fields? A double-blind randomized provocation study.

PubMed

Eltiti, Stacy; Wallace, Denise; Ridgewell, Anna; Zougkou, Konstantina; Russo, Riccardo; Sepulveda, Francisco; Mirshekar-Syahkal, Dariush; Rasor, Paul; Deeble, Roger; Fox, Elaine

2007-11-01

Individuals with idiopathic environmental illness with attribution to electromagnetic fields (IEI-EMF) believe they suffer negative health effects when exposed to electromagnetic fields from everyday objects such as mobile phone base stations. This study used both open provocation and double-blind tests to determine if sensitive and control individuals experience more negative health effects when exposed to base station-like signals compared with sham. Fifty-six self-reported sensitive and 120 control participants were tested in an open provocation test. Of these, 12 sensitive and 6 controls withdrew after the first session. The remainder completed a series of double-blind tests. Subjective measures of well-being and symptoms as well as physiological measures of blood volume pulse, heart rate, and skin conductance were obtained. During the open provocation, sensitive individuals reported lower levels of well-being in both the global system for mobile communication (GSM) and universal mobile telecommunications system (UMTS) compared with sham exposure, whereas controls reported more symptoms during the UMTS exposure. During double-blind tests the GSM signal did not have any effect on either group. Sensitive participants did report elevated levels of arousal during the UMTS condition, whereas the number or severity of symptoms experienced did not increase. Physiological measures did not differ across the three exposure conditions for either group. Short-term exposure to a typical GSM base station-like signal did not affect well-being or physiological functions in sensitive or control individuals. Sensitive individuals reported elevated levels of arousal when exposed to a UMTS signal. Further analysis, however, indicated that this difference was likely to be due to the effect of order of exposure rather than the exposure itself.

Abnormal hip physical examination findings in asymptomatic female soccer athletes

PubMed Central

Hunt, Devyani; Rho, Monica; Yemm, Ted; Fong, Kathryn; Brophy, Robert H.

2016-01-01

Purpose Examination of the hip provides information regarding risk for pre-arthritic hip disorders, knee injuries, and low back pain. The purpose of this study was to report a hip screening examination of asymptomatic female soccer athletes and to test the hypothesis that these findings vary by competition experience. Methods Asymptomatic females from a youth soccer club, a college, and a professional team were evaluated. Passive hip range of motion, hip abduction strength, and hip provocative tests were assessed. Data were compared for the grade/middle school, high school, college, and professional athletes. Results One hundred and seventy-two athletes with a mean age of 16.7 ± 5 years (range 10–30) participated. Professional athletes had less flexion (HF) for both hips (p < 0.0001) and less internal rotation (IR) for the preferred kicking leg (p < 0.05) compared to all other groups. Grade/middle school athletes had more external rotation in both hips as compared to all other groups (p < 0.0001). For the preferred kicking leg, collegiate athletes had less hip abduction strength as compared to other groups (p < 0.01). Positive provocative hip tests were found in 22 % of all players and 36 % of the professionals. In professionals, a positive provocative test was associated with ipsilateral decreased HF (p = 0.04). Conclusion Asymptomatic elite female soccer athletes with the most competition experience had less bilateral hip flexion and preferred kicking leg IR than less-experienced athletes. Positive provocative hip tests were found in 22 % of athletes. Future studies are needed to show whether these findings link to risk for intra-articular hip or lumbar spine and knee disorders. Level of evidence III. PMID:24150125

Does Short-Term Exposure to Mobile Phone Base Station Signals Increase Symptoms in Individuals Who Report Sensitivity to Electromagnetic Fields? A Double-Blind Randomized Provocation Study

PubMed Central

Eltiti, Stacy; Wallace, Denise; Ridgewell, Anna; Zougkou, Konstantina; Russo, Riccardo; Sepulveda, Francisco; Mirshekar-Syahkal, Dariush; Rasor, Paul; Deeble, Roger; Fox, Elaine

2007-01-01

Background Individuals with idiopathic environmental illness with attribution to electromagnetic fields (IEI-EMF) believe they suffer negative health effects when exposed to electromagnetic fields from everyday objects such as mobile phone base stations. Objectives This study used both open provocation and double-blind tests to determine if sensitive and control individuals experience more negative health effects when exposed to base station-like signals compared with sham. Methods Fifty-six self-reported sensitive and 120 control participants were tested in an open provocation test. Of these, 12 sensitive and 6 controls withdrew after the first session. The remainder completed a series of double-blind tests. Subjective measures of well-being and symptoms as well as physiological measures of blood volume pulse, heart rate, and skin conductance were obtained. Results During the open provocation, sensitive individuals reported lower levels of well-being in both the global system for mobile communication (GSM) and universal mobile telecommunications system (UMTS) compared with sham exposure, whereas controls reported more symptoms during the UMTS exposure. During double-blind tests the GSM signal did not have any effect on either group. Sensitive participants did report elevated levels of arousal during the UMTS condition, whereas the number or severity of symptoms experienced did not increase. Physiological measures did not differ across the three exposure conditions for either group. Conclusions Short-term exposure to a typical GSM base station-like signal did not affect well-being or physiological functions in sensitive or control individuals. Sensitive individuals reported elevated levels of arousal when exposed to a UMTS signal. Further analysis, however, indicated that this difference was likely to be due to the effect of order of exposure rather than the exposure itself. PMID:18007992

Topical Non-Iontophoretic Application of Acetylcholine and Nitroglycerin via a Translucent Patch: A New Means for Assessing Microvascular Reactivity

PubMed Central

Schonberger, Robert B.; Worden, William S.; Shahmohammadi, Kaveh; Menn, Kirsten; Silverman, Tyler J.; Stout, Robert G.; Shelley, Kirk H.; Silverman, David G.

2007-01-01

Objective: Assessments of endothelial cell function with acetylcholine have typically used systemic, regional intra-arterial, or iontophoretic delivery of drug. Each of these techniques induces systemic and/or local changes that compromise their safety or effectiveness. Using translucent drug preparations applied under laser Doppler flowmetry (LDF) probes, we tested whether local vasodilation can be induced with non-iontophoretic transdermal delivery of acetylcholine and how such dilation would compare to the dilation achieved with topical nitroglycerin in healthy volunteers. Methods: Ten subjects without known vascular disease were recruited for LDF monitoring at sites of drug application for this preliminary investigation. Topical acetylcholine chloride, nitroglycerin, and placebo were applied via translucent patches to the forehead directly below LDF probes. Results: LDF readings increased by 406 percent (245 percent to 566 percent) and 36 percent (26 percent to 46 percent), respectively, at the acetylcholine and placebo sites (p = .005 by Wilcoxon Signed Rank Test (WSRT) for acetylcholine vs. placebo); and they increased by 365 percent (179 percent to 550 percent) at the nitroglycerin site (p = .005 by WSRT for nitroglycerin vs. placebo; p = .6 vs. acetylcholine). Conclusion: Transdermal delivery of acetylcholine can induce significant local vasodilatory responses comparable to those achieved with nitroglycerin without requiring iontophoresis. The means of transdermal delivery and monitoring described herein may constitute a new minimally invasive way to interrogate the microvasculature and thereby assess the microcirculatory changes induced by various disorders and therapeutic interventions. PMID:17876370

Evaluation of colonoscopic allergen provocation as a diagnostic tool in dogs with proven food hypersensitivity reactions.

PubMed

Allenspach, K; Vaden, S L; Harris, T S; Gröne, A; Doherr, M G; Griot-Wenk, M E; Bischoff, S C; Gaschen, F

2006-01-01

To evaluate the colonoscopic allergen provocation (COLAP) test as a new tool for the diagnosis of IgE-mediated food allergy. Oral food challenges as well as COLAP testing were performed in a colony of nine research dogs with proven immediate-type food allergic reactions. In addition, COLAP was performed in five healthy dogs. When compared with the oral challenge test, COLAP accurately determined 18 of 23 (73 per cent) positive oral challenge reactions (73 per cent) in dogs with food allergies and was negative in the healthy dogs. The accuracy of this new test may be higher than that for gastric sensitivity testing. Therefore, COLAP holds promise as a new test to confirm the diagnosis of suspect IgE-mediated food allergy in dogs.

Oxytocin strengthens the link between provocation and aggression among low anxiety people.

PubMed

Pfundmair, Michaela; Reinelt, Annika; DeWall, C Nathan; Feldmann, Lisa

2018-07-01

Oxytocin (OT) not only modulates positive social interactions but also affects negative ones. Several studies have established a link between OT and aggression. However, they also resulted in an inconsistent picture and showed methodological issues. The current studies aimed to address these lacks and test the hypothesis that OT increases provocation-induced aggression in people low in anxiety. Therefore, two studies with 56 males (Study 1) as well as 40 females and 24 males (Study 2) were conducted. After responding to a trait anxiety questionnaire, participants self-administered OT or a placebo. Thereafter, provocation was manipulated by rejecting vs. accepting (Study 1) or insulting vs. accepting (Study 2) the participants by real human counterparts. Aggressive behavior was quantified by measuring how much hot sauce (Study 1) or unpleasant blasts of white noise (Study 2) participants delivered to their opponents, using two classic aggression paradigms. Both studies provided evidence that OT promotes aggression in response to provocation in low anxiety people which was not the case with no provocation or in high anxiety people. These findings confirm the idea that OT can be involved in the creation of aggressive behavior when accounting for situational and dispositional features. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Role of acetylcholine in gelsenicine-induced death in mice].

PubMed

Lai, Zhou-Yi; Wang, Hai-Bo; Lv, Rui-Ling; Tan, Qiu-Chan; Deng, Zhi-Qin; Wang, Yuan; Sun, Xiao-Xue; Wu, Jia-Bao; Zhu, Lin-Yan; Wang, Lei; Chen, Li-Xin; Ye, Wen-Cai; Wang, Li-Wei

2016-06-25

The aim of this study was to investigate the relationship between the acetylcholine concentration in the blood and gelsenicine-induced death in mice. Kunming mice were given intraperitoneal injections of normal saline, gelsenicine or different doses of acetylcholine chloride. Atropine was given to the mice which received gelsenicine or medium dose acetylcholine chloride injection. The blood was sampled immediately when the mice died or survived for 20 min after injection. The acetylcholine concentration and acetylcholinesterase activity in the blood were measured by the testing kits, and the mortality was calculated and analyzed. The results showed that half lethal dose of gelsenicine (0.15 mg/kg) reduced the acetylcholinesterase activity and increased the blood acetylcholine concentration. The blood acetylcholine concentration of the dead mice in the gelsenicine group was increased to 43.0 μg/mL (from 31.1 μg/mL in the control), which was lower than that (53.9 μg/mL) of the dead mice in the medium dose acetylcholine chloride group, but almost equal to that (42.7 μg/mL) of the survival mice in the medium dose acetylcholine chloride group. Atropine could successfully rescue the mice from acetylcholine poisoning, but its efficiency of rescuing the mice from gelsenicine intoxication was weak. These results suggest that gelsenicine can inhibit acetylcholinesterase activity and increase blood acetylcholine concentration, but the accumulation of acetylcholine may not be the only or main cause of the death induced by gelsenicine in mice.

Localized periorbital edema as a clinical manifestation of sulfite sensitivity.

PubMed

Park, H S; Nahm, D

1996-08-01

Sulfite is commonly used in pharmaceuticals as a preservative. We report a unique clinical presentation of localized periorbital edema on the left eye after administration of sulfite-containing dexamethasone. The patient's sulfite sensitivity was confirmed by sulfite oral provocation test: periorbital edema on the same site developed after ingestion of 200 mg sodium bisulfite. She was non-atopic and did not complain of any respiratory symptoms. Allergy skin prick test with 100 mg/ml sodium bisulfite showed a negative result. She also has aspirin-sensitive urticaria which was confirmed by oral provocation test. In conclusion, sulfite can induce a localized periorbital edema, an uncommon manifestation in sensitive patients. Further investigations are needed to clarify the pathogenetic mechanisms.

Cholinestrase test (image)

MedlinePlus

... The sample is taken to the laboratory for evaluation. The lab evaluates the enzymes acetylcholinesterase and pseudocholinesterase, which act to break down acetylcholine. Acetylcholine is a critical chemical in the transmission of nerve impulses.

Acetylcholine receptor antibody

MedlinePlus

... found in the blood of most people with myasthenia gravis . The antibody affects a chemical that sends signals ... Performed This test is used to help diagnose myasthenia gravis . Normal Results Normally, there is no acetylcholine receptor ...

Difference Between Dormant Conduction Sites Revealed by Adenosine Triphosphate Provocation and Unipolar Pace-Capture Sites Along the Ablation Line After Pulmonary Vein Isolation.

PubMed

Kogawa, Rikitake; Okumura, Yasuo; Watanabe, Ichiro; Sonoda, Kazumasa; Sasaki, Naoko; Takahashi, Keiko; Iso, Kazuki; Nagashima, Koichi; Ohkubo, Kimie; Nakai, Toshiko; Kunimoto, Satoshi; Hirayama, Atsushi

2016-01-01

Dormant pulmonary vein (PV) conduction revealed by adenosine/adenosine triphosphate (ATP) provocation test and exit block to the left atrium by pacing from the PV side of the ablation line ("pace and ablate" method) are used to ensure durable pulmonary vein isolation (PVI). However, the mechanistic relation between ATP-provoked PV reconnection and the unexcitable gap along the ablation line is unclear.Forty-five patients with atrial fibrillation (AF) (paroxysmal: 31 patients, persistent: 14 patients; age: 61.1 ± 9.7 years) underwent extensive encircling PVI (EEPVI, 179 PVs). After completion of EEPVI, an ATP provocation test (30 mg, bolus injection) and unipolar pacing (output, 10 mA; pulse width, 2 ms) were performed along the previous EEPVI ablation line to identify excitable gaps. Dormant conduction was revealed in 29 (34 sites) of 179 PVs (16.2%) after EEP-VI (22/45 patients). Pace capture was revealed in 59 (89 sites) of 179 PVs (33.0%) after EEPVI (39/45 patients), and overlapping sites, ie, sites showing both dormant conduction and pace capture, were observed in 22 of 179 (12.3%) PVs (17/45 patients).Some of the ATP-provoked dormant PV reconnection sites were identical to the sites with excitable gaps revealed by pace capture, but most of the PV sites were differently distributed, suggesting that the main underling mechanism differs between these two forms of reconnection. These findings also suggest that performance of the ATP provocation test followed by the "pace and ablate" method can reduce the occurrence of chronic PV reconnections.

Exogenous Testosterone Enhances the Reactivity to Social Provocation in Males

PubMed Central

Wagels, Lisa; Votinov, Mikhail; Kellermann, Thilo; Eisert, Albrecht; Beyer, Cordian; Habel, Ute

2018-01-01

Testosterone affects human social behavior in various ways. While testosterone effects are generally associated with muscular strength and aggressiveness, human studies also point towards enhanced status–seeking motives after testosterone administration. The current study tested the causal influence of exogenous testosterone on male behavior during a competitive provocation paradigm. In this double blind, randomized, placebo (PL)-controlled study, 103 males were assigned to a PL or testosterone group receiving a colorless PL or testosterone gel. To induce provocation, males played a rigged reaction time game against an ostensible opponent. When participants lost, the opponent subtracted money from the participant who in return could subtract money from the ostensible opponent. Participants subjectively indicated anger and self-estimated treatment affiliation (testosterone or PL administration). A trial-by-trial analysis demonstrated that provocation and success during the repeated games had a stronger influence on participants’ choice to reduce money from the opponent if they had received testosterone. Participants who believed to be in the testosterone group were angrier after the experiment and increased monetary reductions during the task course. In line with theories about mechanisms of testosterone in humans, provocation is shown to be necessary for the agency of exogenous testosterone. Thus, testosterone reinforces the conditional adjustment of aggressive behavior but not aggressive behavior per se. In contrast undirected frustration is not increased by testosterone but probably interferes with cognitive appraisals about biological mechanisms of testosterone. PMID:29551966

Exogenous Testosterone Enhances the Reactivity to Social Provocation in Males.

PubMed

Wagels, Lisa; Votinov, Mikhail; Kellermann, Thilo; Eisert, Albrecht; Beyer, Cordian; Habel, Ute

2018-01-01

Testosterone affects human social behavior in various ways. While testosterone effects are generally associated with muscular strength and aggressiveness, human studies also point towards enhanced status-seeking motives after testosterone administration. The current study tested the causal influence of exogenous testosterone on male behavior during a competitive provocation paradigm. In this double blind, randomized, placebo (PL)-controlled study, 103 males were assigned to a PL or testosterone group receiving a colorless PL or testosterone gel. To induce provocation, males played a rigged reaction time game against an ostensible opponent. When participants lost, the opponent subtracted money from the participant who in return could subtract money from the ostensible opponent. Participants subjectively indicated anger and self-estimated treatment affiliation (testosterone or PL administration). A trial-by-trial analysis demonstrated that provocation and success during the repeated games had a stronger influence on participants' choice to reduce money from the opponent if they had received testosterone. Participants who believed to be in the testosterone group were angrier after the experiment and increased monetary reductions during the task course. In line with theories about mechanisms of testosterone in humans, provocation is shown to be necessary for the agency of exogenous testosterone. Thus, testosterone reinforces the conditional adjustment of aggressive behavior but not aggressive behavior per se . In contrast undirected frustration is not increased by testosterone but probably interferes with cognitive appraisals about biological mechanisms of testosterone.

Localized periorbital edema as a clinical manifestation of sulfite sensitivity.

PubMed Central

Park, H. S.; Nahm, D.

1996-01-01

Sulfite is commonly used in pharmaceuticals as a preservative. We report a unique clinical presentation of localized periorbital edema on the left eye after administration of sulfite-containing dexamethasone. The patient's sulfite sensitivity was confirmed by sulfite oral provocation test: periorbital edema on the same site developed after ingestion of 200 mg sodium bisulfite. She was non-atopic and did not complain of any respiratory symptoms. Allergy skin prick test with 100 mg/ml sodium bisulfite showed a negative result. She also has aspirin-sensitive urticaria which was confirmed by oral provocation test. In conclusion, sulfite can induce a localized periorbital edema, an uncommon manifestation in sensitive patients. Further investigations are needed to clarify the pathogenetic mechanisms. PMID:8878807

Assessment of Social Information Processing in early childhood: development and initial validation of the Schultz Test of Emotion Processing-Preliminary Version.

PubMed

Schultz, David; Ambike, Archana; Logie, Sean Kevin; Bohner, Katherine E; Stapleton, Laura M; Vanderwalde, Holly; Min, Christopher B; Betkowski, Jennifer A

2010-07-01

Crick and Dodge's (Psychological Bulletin 115:74-101, 1994) social information processing model has proven very useful in guiding research focused on aggressive and peer-rejected children's social-cognitive functioning. Its application to early childhood, however, has been much more limited. The present study responds to this gap by developing and validating a video-based assessment tool appropriate for early childhood, the Schultz Test of Emotion Processing-Preliminary Version (STEP-P). One hundred twenty-five Head Start preschool children participated in the study. More socially competent children more frequently attributed sadness to the victims of provocation and labeled aggressive behaviors as both morally unacceptable and less likely to lead to positive outcomes. More socially competent girls labeled others' emotions more accurately. More disruptive children more frequently produced physically aggressive solutions to social provocations, and more disruptive boys less frequently interpreted social provocations as accidental. The STEP-P holds promise as an assessment tool that assesses knowledge structures related to the SIP model in early childhood.

May nasal hyperreactivity be a sequela of recurrent common cold?

PubMed

Cassano, M; Cassano, P; Ciprandi, G

2011-01-01

Respiratory viral infections may worsen bronchial hyperreactivity. However, there is no data on the possible role of recurrent infectious rhinitis in nose hyperreactivity. This study was therefore designed to investigate whether subjects suffering from recurrent common cold have nasal hyperreactivity, assessed by histamine nasal challenge. This study included a group of 40 patients (19 males, mean age 34.1 years) with history of at least five episodes of common cold in the previous year, but without documented allergy, and twenty healthy subjects (8 males, mean age 32.3 years) were enrolled as control group, all of whom were non-allergic. Nasal provocation test with histamine was performed in all subjects. Nasal provocation test with histamine induced a 200% increase in nasal resistance after provocation in 24 (60%) patients suffering from recurrent viral rhinitis. No normal subject had an increase >180% in nasal resistance. There was a significant difference between the patient group and the control group (p<0.05). In conclusion, this study shows that nasal hyperreactivity might be a sequela of recurrent common cold. Further studies should be conducted to confirm this preliminary finding.

Self-reported dietary fructose intolerance in irritable bowel syndrome: Proposed diagnostic criteria.

PubMed

Berg, Leif Kyrre; Fagerli, Erik; Myhre, Arnt-Otto; Florholmen, Jon; Goll, Rasmus

2015-05-14

To study the criteria for self-reported dietary fructose intolerance (DFI) and to evaluate subjective global assessment (SGA) as outcome measure. Irritable bowel syndrome (IBS) patients were randomized in an open study design with a 2 wk run-in on a habitual IBS diet, followed by 12 wk with/without additional fructose-reduced diet (FRD). Daily registrations of stool frequency and consistency, and symptoms on a visual analog scale (VAS) were performed during the first 4 wk. SGA was used for weekly registrations during the whole study period. Provocation with high-fructose diet was done at the end of the registration period. Fructose breath tests (FBTs) were performed. A total of 182 subjects performed the study according to the protocol (88 FRD, 94 controls). We propose a new clinically feasible diagnostic standard for self-reported fructose intolerance. The instrument is based on VAS registrations of symptom relief on FRD combined with symptom aggravation upon provocation with fructose-rich diet. Using these criteria 43 of 77 patients (56%) in the present cohort of IBS patients had self-reported DFI. To improve the concept for clinical evaluation, we translated the SGA scale instrument to Norwegian and validated it in the context of the IBS diet regimen. The validation procedures showed a sensitivity, specificity and κ value for SGA detecting the self-reported DFI group by FRD response within the IBS patients of 0.79, 0.75 and 0.53, respectively. Addition of the provocation test yielded values of 0.84, 0.76 and 0.61, respectively. The corresponding validation results for FBT were 0.57, 0.34 and -0.13, respectively. FRD improves symptoms in a subgroup of IBS patients. A diet trial followed by a provocation test evaluated by SGA can identify most responders to FRD.

Comparison of capnovolumetry-derived dead space parameters with pulmonary function test in normal adults using histamine provocation.

PubMed

Sun, Xiaoli; Zhang, Yan; Yang, Wenlan; Liu, Jinming

2015-04-01

This study in healthy adults was conducted to explore the clinical application of capnovolumetric indices as compared to lung function parameters using histamine provocation. Forty healthy subjects received aerosol histamine or salbutamol in an automatic stimulation system with escalating doses of histamine. Dead space volumes of capnovolumetry and lung function parameters were examined with increased concentrations of histamine at a fixed time interval. The doses of histamine were selected from 0.0562 mg-2.2 mg and 0.1 mg salbutamol was inhaled when a maximal dose of histamine was reached. Baseline values in each group were calculated prior to histamine inhalation. Fowler dead space (VDF), Wolff dead space (VDW), threshold dead space (VDT), Bohr dead space (VDB), forced expiratory volume in 1 s (FEV1 ) and peak expiratory flow (PEF) showed a dose-dependent reduction following histamine provocation, but there were no statistical differences in the measurements at baseline and post S6 provocation. The value of dC3/DV at the maximal dose was significantly increased over its baseline value (P < 0.05). VDF, VDT and VDW were significantly increased after bronchodilator use (P < 0.05 or <0.01). The changes in capnovolumetry did not correspond with the results of lung function test. The dC3/DV and airway dead spaces of capnovolumetry in healthy adults are significantly increased compared to lung function parameters before or after bronchodilator use, suggesting that capnovolumetry is feasible in diagnostic evaluation of airway reactivity, especially for persons who are unable to undertake lung function test. © 2014 John Wiley & Sons Ltd.

De-labelling self-reported penicillin allergy within the emergency department through the use of skin tests and oral drug provocation testing.

PubMed

Marwood, Joseph; Aguirrebarrena, Gonzalo; Kerr, Stephen; Welch, Susan A; Rimmer, Janet

2017-10-01

Self-reported penicillin allergy is common among patients attending the ED, but is a poor predictor of true immunoglobulin E-mediated hypersensitivity to penicillin. We hypothesise that with a combination of skin testing and drug provocation testing, selected patients can be safely de-labelled of their allergy. This prospective study enrolled a sample of patients presenting to an urban academic ED between 2011 and 2016 with a self-reported allergy to penicillin. Standardised skin prick and intradermal testing with amoxicillin and both major and minor determinants of penicillin was performed in the department. If negative, testing was followed by a graded oral challenge of amoxicillin over 9 days. The primary end point was the allergy status of participants at the end of the study. A total of 100 patients (mean age 42; standard deviation 14 years; 54% women) completed the testing. Of these, 81% (95% confidence interval 71.9-88.2) showed no hypersensitivity to penicillin and were labelled non-allergic. The majority (16/19) of allergies were confirmed by skin testing, with three suspected allergies detected by the oral challenge. Women were more likely than men to have a true penicillin allergy, with odds ratio of 4.0 (95% confidence interval 1.23-13.2). There were no serious adverse events. Selected patients in the ED who self-report an allergy to penicillin can be safely tested there for penicillin allergy, using skin tests and oral drug provocation testing. This testing allows a significant de-labelling of penicillin allergy, with the majority of these patients able to tolerate penicillin without incident. © 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Evidence-Based Diagnosis and Treatment of the Painful Sacroiliac Joint

PubMed Central

Laslett, Mark

2008-01-01

Sacroiliac joint (SIJ) pain refers to the pain arising from the SIJ joint structures. SIJ dysfunction generally refers to aberrant position or movement of SIJ structures that may or may not result in pain. This paper aims to clarify the difference between these clinical concepts and present current available evidence regarding diagnosis and treatment of SIJ disorders. Tests for SIJ dysfunction generally have poor inter-examiner reliability. A reference standard for SIJ dysfunction is not readily available, so validity of the tests for this disorder is unknown. Tests that stress the SIJ in order to provoke familiar pain have acceptable inter-examiner reliability and have clinically useful validity against an acceptable reference standard. It is unknown if provocation tests can reliably identify extra-articular SIJ sources of pain. Three or more positive pain provocation SIJ tests have sensitivity and specificity of 91% and 78%, respectively. Specificity of three or more positive tests increases to 87% in patients whose symptoms cannot be made to move towards the spinal midline, i.e., centralize. In chronic back pain populations, patients who have three or more positive provocation SIJ tests and whose symptoms cannot be made to centralize have a probability of having SIJ pain of 77%, and in pregnant populations with back pain, a probability of 89%. This combination of test findings could be used in research to evaluate the efficacy of specific treatments for SIJ pain. Treatments most likely to be effective are specific lumbopelvic stabilization training and injections of corticosteroid into the intra-articular space. PMID:19119403

Ondansetron and promethazine have differential effects on hypothermic responses to lithium chloride administration and to provocative motion in rats

PubMed Central

Guimaraes, Drielle D; Andrews, Paul L R; Rudd, John A; Braga, Valdir A; Nalivaiko, Eugene

2015-01-01

We recently reported that provocative motion (rotation in a home cage) causes hypothermic responses in rats, similar to the hypothermic responses associated with motion sickness in humans. Many stimuli inducing emesis in species with an emetic reflex also provoke hypothermia in the rat, therefore we hypothesized that a fall in body temperature may reflect a “nausea-like” state in these animals. As rats do not possess an emetic reflex, we employed a pharmacological approach to test this hypothesis. In humans, motion- and chemically-induced nausea have differential sensitivity to anti-emetics. We thus tested whether the hypothermia induced in rats by provocative motion (rotation at 0.7 Hz) and by the emetic LiCl (63 mg/kg i.p.) have a similar differential pharmacological sensitivity. Both provocations caused a comparable robust fall in core body temperature (−1.9 ± 0.3°C and −2.0 ± 0.2°C for chemical and motion provocations, respectively). LiCl−induced hypothermia was completely prevented by ondansetron (2mg/kg, i.p., a 5-HT3 receptor antagonist that reduces cancer chemotherapy-induced nausea and vomiting), but was insensitive to promethazine (10 mg/kg, i.p., a predominantly histamine-H1 and muscarinic receptor antagonist that is commonly used to treat motion sickness). Conversely, motion-induced hypothermia was unaffected by ondansetron but promethazine reduced the rate of temperature decline from 0.20 ± 0.02 to 0.11 ± 0.03°C/min (P < 0.05) with a trend to decrease the magnitude. We conclude that this differential pharmacological sensitivity of the hypothermic responses of vestibular vs. chemical etiology in rats mirrors the observations in other pre-clinical models and humans, and thus supports the idea that a “nausea-like” state in rodents is associated with disturbances in thermoregulation. PMID:27227074

Scopolamine provocation-based pharmacological MRI model for testing procognitive agents.

PubMed

Hegedűs, Nikolett; Laszy, Judit; Gyertyán, István; Kocsis, Pál; Gajári, Dávid; Dávid, Szabolcs; Deli, Levente; Pozsgay, Zsófia; Tihanyi, Károly

2015-04-01

There is a huge unmet need to understand and treat pathological cognitive impairment. The development of disease modifying cognitive enhancers is hindered by the lack of correct pathomechanism and suitable animal models. Most animal models to study cognition and pathology do not fulfil either the predictive validity, face validity or construct validity criteria, and also outcome measures greatly differ from those of human trials. Fortunately, some pharmacological agents such as scopolamine evoke similar effects on cognition and cerebral circulation in rodents and humans and functional MRI enables us to compare cognitive agents directly in different species. In this paper we report the validation of a scopolamine based rodent pharmacological MRI provocation model. The effects of deemed procognitive agents (donepezil, vinpocetine, piracetam, alpha 7 selective cholinergic compounds EVP-6124, PNU-120596) were compared on the blood-oxygen-level dependent responses and also linked to rodent cognitive models. These drugs revealed significant effect on scopolamine induced blood-oxygen-level dependent change except for piracetam. In the water labyrinth test only PNU-120596 did not show a significant effect. This provocational model is suitable for testing procognitive compounds. These functional MR imaging experiments can be paralleled with human studies, which may help reduce the number of false cognitive clinical trials. © The Author(s) 2015.

Outcomes of a pilates-based intervention for individuals with lateral epicondylosis: A pilot study.

PubMed

Dale, Lucinda M; Mikuski, Connie; Miller, Jacqueline

2015-01-01

Core stability and flexibility, features of Pilates exercise, can reduce loads to the upper extremities. Reducing loads is essential to improve symptoms for individuals with lateral epicondylosis. Although Pilates exercise has gained popularity in healthy populations, it has not been studied for individuals with lateral epicondylosis. The purpose of this study was to determine if adding Pilates-based intervention to standard occupational therapy intervention improved outcomes as measured by the Patient-Rated Tennis Elbow Evaluation (PRTEE) more than standard intervention for individuals with lateral epicondylosis. Participants (N= 17) were randomized to the standard intervention group or Pilates-based intervention group. All participants received standard intervention. The Pilates-based intervention group additionally completed abdominal strengthening, postural correction, and flexibility. For both groups, paired t-tests showed significantly improved PRTEE scores, 38.1 for the Pilates-based intervention group, and 22.9 for the standard intervention group. Paired t-test showed significantly improved provocative grip strength and pain for both groups. Independent t-tests showed no significant difference between groups in improved scores of PRTEE, pain, and provocative grip. Although the Pilates-based intervention group showed greater improvement in PRTEE outcome, provocative grip, and pain, scores were not significantly better than those of the standard intervention group, warranting further research.

Serotonin Augmentation Reduces Response to Attack in Aggressive Individuals

PubMed Central

Berman, Mitchell E.; McCloskey, Michael S.; Fanning, Jennifer R.; Schumacher, Julie A.; Coccaro, Emil F.

2009-01-01

We tested the theory that central serotonin (5- hydroxytryptamine, or 5-HT) activity regulates aggression by modulating response to provocation. Eighty men and women (40 with and 40 without a history of aggression) were randomly assigned to receive either 40 mg of paroxetine (to acutely augment serotonergic activity) or a placebo, administered using double-blind procedures. Aggression was assessed during a competitive reaction time game with a fictitious opponent. Shocks were selected by the participant and opponent before each trial, with the loser on each trial receiving the shock set by the other player. Provocation was manipulated by having the opponent select increasingly intense shocks for the participant and eventually an ostensibly severe shock toward the end of the trials. Aggression was measured by the number of severe shocks set by the participant for the opponent. As predicted, aggressive responding after provocation was attenuated by augmentation of serotonin in individuals with a pronounced history of aggression. PMID:19422623

The situation specificity of youth responses to peer provocation.

PubMed

Dirks, Melanie A; Treat, Teresa A; Weersing, V Robin

2007-01-01

Previous studies have identified peer provocation as a challenging class of situations for youth. The work presented here builds on previous methods of assessing peer provocation by (a) increasing the contextual detail of the vignettes; (b) developing a reliable, descriptive coding system of the range of youth responses to physical, verbal, and relational provocation; and (c) assessing the relevance of these situations for a sample (N = 76) of ethnically diverse, economically disadvantaged youth ages 12 to 14. The vignettes were used to examine the situation specificity of youth responses to provocation. Situation and identity of aggressor were both predictors of youth responses. For example, participants "matched" physical aggression to physical provocation. These findings are consistent with previous studies demonstrating the situation specificity of social information processing, even within the relatively homogeneous category of peer provocations.

Natural History of Benign Nonimmediate Allergy to Beta-Lactams in Children: A Prospective Study in Retreated Patients After a Positive and a Negative Provocation Test.

PubMed

Tonson la Tour, Aude; Michelet, Marine; Eigenmann, Philippe A; Caubet, Jean-Christoph

2017-11-23

The drug provocation test (DPT) is considered as the gold standard to diagnose drug allergy and is particularly important in the diagnosis of nonimmediate beta-lactam (BL) allergy in children. The natural history of BL allergy remains unknown. Our main aim was to evaluate the natural history of nonimmediate BL hypersensitivity and the long-term tolerance acquisition, and our secondary objective was to determine the negative predictive value (NPV) of the DPT following a 2-day protocol. Children developing a benign rash while treated by BL were prospectively recruited at the Emergency Department of the Geneva University Hospital from 2006 to 2011 and challenged with the incriminated BL (initial diagnostic drug provocation test [idDPT]) following a 2-day protocol. In case of a positive idDPT, the patients underwent a follow-up drug provocation test (fuDPT) 3 years later. In case of a negative idDPT, we sent a questionnaire to assess tolerance of a subsequent treatment with the incriminated BL. Among the 18 children with a positive idDPT, 16 children (89%) had a negative fuDPT and 2 children developed a benign exanthema. Among those 16 children, 11 tolerated a subsequent treatment with the incriminated BL without any reaction, suggesting natural antibiotic tolerance acquisition. From another point of view, we found that the NPV of the DPT following a 2-day protocol was excellent at 96.7%. Our data strongly suggest that a fuDPT is safe and useful to assess tolerance acquisition in children with a confirmed benign nonimmediate BL allergy. In addition, our results support the use of a short DPT protocol (2 days), which led to a high NPV of 96.7% in our population, with a favorable benefit-risk balance. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Empathy Inhibits Aggression in Competition: The Role of Provocation, Emotion, and Gender.

PubMed

Stanger, Nicholas; Kavussanu, Maria; McIntyre, David; Ring, Christopher

2016-02-01

Although the empathy-aggression relationship has been well documented, research has yet to establish whether emotions mediate and gender moderates this relationship in athletes, under conditions of low and high provocation. In this experiment, we assigned team-sport athletes to either a high (n = 40) or a low (n = 40) empathy group, and asked them to compete in a reaction-time task against a (fictitious) opponent, under conditions of low and high provocation. Empathy reduced aggression (i.e., intensity of electrical shock administered to the opponent) at low provocation in men, and at both low and high provocation in women. Guilt mediated the effect of empathy on aggression at low provocation in men; anger did not mediate any effects of empathy on aggression. Our findings indicate that the inhibitory effect of empathy on aggression and the mediating role of guilt are moderated by provocation and gender.

The susceptibility of rhesus monkeys to motion sickness

NASA Technical Reports Server (NTRS)

Corcoran, Meryl L.; Daunton, Nancy G.; Fox, Robert A.

1990-01-01

The susceptibility of rhesus monkeys to motion sickness was investigated using test conditions that are provocative for eliciting motion sickness in squirrel monkeys. Ten male rhesus monkeys and ten male Bolivian squirrel monkeys were rotated in the vertical axis at 150 deg/s for a maximum duration of 45 min. Each animal was tested in two conditions, continuous rotation and intermittent rotation. None of the rhesus monkeys vomited during the motion tests but all of the squirrel monkeys did. Differences were observed between the species in the amount of activity that occurred during motion test, with the squirrel monkeys being significantly more active than the rhesus monkeys. These results, while substantiating anecdotal reports of the resistance of rhesus monkeys to motion sickness, should be interpreted with caution because of the documented differences that exist between various species with regard to stimuli that are provocative for eliciting motion sickness.

Intravenously administered oxotremorine and atropine, in doses known to affect pain threshold, affect the intraspinal release of acetylcholine in rats.

PubMed

Abelson, Klas S P; Höglund, A Urban

2002-04-01

Both systemically and intrathecally administered cholinergic agonists produce antinociception while cholinergic antagonists decrease pain threshold. The mechanism and the site of action of these substances are not known. In the present study it was hypothesized that systemically administered muscarinic agonists and antagonists modify nociceptive threshold by affecting intraspinal release of acetylcholine (ACh). Catheters were inserted into the femoral vein in rats maintained on isoflurane anaesthesia for administration of oxotremorine (10-300 microg/kg) and atropine (0.1, 10, 5000 microg/kg). Spinal microdialysis probes were placed intraspinally at approximately the C2-C5 spinal level for sampling of acetylcholine and dialysis delivery of atropine (0.1, 1, 10 nM). Additionally, the tail-flick behaviour was tested on conscious rats injected intraperitoneally with saline, atropine (10, 100 and 5000 microg/kg), or subcutaneously with oxotremorine (30, 100, 300 microg/kg). Subcutaneous administration of oxotremorine (30, 100, 300 microg/kg) significantly increased the tail-flick latency. These doses of oxotremorine dose-dependently increased the intraspinal release of acetylcholine. Intravenously administered atropine, in a dose that produced hyperalgesia (5000 microg/kg) in the tail-flick test, significantly decreased the intraspinal release of acetylcholine. Our results suggest an association between pain threshold and acetylcholine release in spinal cord. It is also suggested that an approximately 30% increase in basal ACh release produces antinociception and that a 30% decrease in basal release produces hyperalgesia.

The effects of postnatal alcohol exposure and galantamine on the context pre-exposure facilitation effect and acetylcholine efflux using in vivo microdialysis

PubMed Central

Perkins, Amy E.; Fadel, Jim R.; Kelly, Sandra J.

2015-01-01

Fetal alcohol spectrum disorders (FASD) affect 2–5% of children. FASD have been shown to cause damage to multiple brain regions, but damage to the hippocampus specifically may explain deficits in learning and memory that are hallmark symptoms of FASD. The acetylcholine neurotransmitter system is a major input to the hippocampus and is a possible target of developmental alcohol exposure. Alcohol (3.0 g/kg/day) was administered via intragastric intubation to developing male rat pups (postnatal day [PD] 2–10; ethanol-treated [ET]), with controls receiving a sham intubation (IC) or no treatment (NC). In Experiment 1, in vivo microdialysis was used to measure acetylcholine efflux in adolescents (PD 32–35). During microdialysis, the effects of a high K+/Ca2+ aCSF solution (PD 32–33) and an acute galantamine (acetylcholinesterase [AChE] inhibitor) injection (2.0 mg/kg; PD 34–35) on acetylcholine efflux were measured. Alcohol-exposed animals did not differ in acetylcholine efflux at baseline. However, alcohol-exposed animals had a decrease in K+/Ca2+-induced acetylcholine efflux compared to non-treated controls, and an enhanced acetylcholine response to galantamine compared to both control groups. Experiment 2 tested whether chronic administration of galantamine (2.0 mg/kg; PD 11–30) could attenuate alcohol-induced learning deficits in the context pre-exposure facilitation effect (CPFE; PD 30–32). Neither chronic galantamine nor postnatal alcohol exposure influenced performance in the CPFE task. Immunohistochemistry was used to measure expression of choline acetyltransferase (ChAT; medial septum), vesicular acetylcholine transporter (vAChT; ventral CA1), and the alpha7 nicotinic acetylcholine receptor (α7 nAChR; ventral CA1) following microdialysis (Exp. 1) or chronic galantamine and behavioral testing (Exp. 2). Neither alcohol exposure nor behavioral testing significantly altered the density of vAChT or α7 nAChRs in the ventral CA1 region of the hippocampus. The average number of ChAT+ cells was increased in the ET animals that displayed the context-shock association; there were no changes in the IC and NC animals that learned the context-shock association or in any of the animals that were in the control task that entailed no learning. Taken together, these results indicate that the hippocampal acetylcholine system is significantly disrupted under conditions of pharmacological manipulations (e.g., galantamine) in alcohol-exposed animals. Furthermore, ChAT was up-regulated in alcohol-exposed animals that learned to associate the context and shock, which may account for their ability to perform this task. Developmental alcohol exposure may disrupt learning and memory in adolescence via a cholinergic mechanism. PMID:25837482

Treatment of pregnancy-related lumbar and pelvic girdle pain by the yoga method: a randomized controlled study.

PubMed

Martins, Roseny Flávia; Pinto e Silva, João Luiz

2014-01-01

Pregnancy-related lumbopelvic pain is a major problem for the majority of pregnant women. Complementary medicine has been used to alleviate pain, and yoga is one of the most commonly chosen alternative methods. The objective of this study was to assess the effectiveness of Hatha yoga in the reduction of lumbopelvic pain in pregnancy. A randomized controlled trial with 60 pregnant women (age range, 14-40 years) who reported lumbopelvic pain at 12 to 32 weeks of gestation was conducted from June 2009 to June 2011. Pregnant women who had twin pregnancies, had medical restrictions for exercise, used analgesics, and participated in physical therapy were excluded from the study. Pregnant women were divided into two groups: the yoga group, practicing exercises guided by this method, and the postural orientation group, performing standardized posture orientation according to instructions provided in a pamphlet. Treatment in each group lasted 10 weeks. A visual analog scale (VAS) was used to measure pain intensity. Lumbar pain and posterior pelvic pain provocation tests were used to confirm the presence of pain. Statistical analysis included the Mann-Whitney test, the McNemar test, a paired Wilcoxon test, and analysis of covariance. The median pain score was lower in the yoga group (p<.0058) than the postural orientation group. Lumbar pain provocation tests showed a decreased response in relation to posterior pelvic pain provocation tests and a gradual reduction in pain intensity during 10 yoga sessions (p<.024). The yoga method was more effective at reducing lumbopelvic pain intensity compared with postural orientation.

Neural response in obsessive-compulsive washers depends on individual fit of triggers

PubMed Central

Baioui, Ali; Pilgramm, Juliane; Merz, Christian J.; Walter, Bertram; Vaitl, Dieter; Stark, Rudolf

2013-01-01

Background: Patients with obsessive-compulsive disorder (OCD) have highly idiosyncratic triggers. To fully understand which role this idiosyncrasy plays in the neurobiological mechanisms behind OCD, it is necessary to elucidate the impact of individualization regarding the applied investigation methods. This functional magnetic resonance imaging (fMRI) study explores the neural correlates of contamination/washing-related OCD with a highly individualized symptom provocation paradigm. Additionally, it is the first study to directly compare individualized and standardized symptom provocation. Methods: Nineteen patients with washing compulsions created individual OCD hierarchies, which later served as instructions to photograph their own individualized stimulus sets. The patients and 19 case-by-case matched healthy controls participated in a symptom provocation fMRI experiment with individualized and standardized stimulus sets created for each patient. Results: OCD patients compared to healthy controls displayed stronger activation in the basal ganglia (nucleus accumbens, nucleus caudatus, pallidum) for individualized symptom provocation. Using standardized symptom provocation, this group comparison led to stronger activation in the nucleus caudatus. The direct comparison of between-group effects for both symptom provocation approaches revealed stronger activation of the orbitofronto-striatal network for individualized symptom provocation. Conclusions: The present study provides insight into the differential impact of individualized and standardized symptom provocation on the orbitofronto-striatal network of OCD washers. Behavioral and neural responses imply a higher symptom-specificity of individualized symptom provocation. PMID:23630478

Intimate partner violence perpetration corresponds to a dorsal-ventral gradient in medial PFC reactivity to interpersonal provocation.

PubMed

Chester, David S; DeWall, C Nathan

2018-01-22

Intimate partner violence (IPV) perpetration is often preceded by perceived interpersonal provocations such as slights, insults, and rejections. Yet the neural mechanisms that link provocation to IPV remain unclear. In the context of interactions with strangers, the medial prefrontal cortex (MPFC) has been repeatedly shown to respond to provocation, with more dorsal activation associated with more aggressive reactions and more ventral activation associated with less aggressive reactions. We used functional brain imaging to test whether this dorsal-ventral MPFC reactivity gradient would also correlate with greater aggression towards an unexamined target: intimate partners. To do so, 61 undergraduates (27.87% male, age range: 18-22) reported whether they had ever committed various acts of IPV perpetration (e.g., punching, hitting, shoving) and then were repeatedly provoked by a stranger while undergoing functional MRI (fMRI) scanning. Individuals with a disproportionately dorsal, rather than ventral, MPFC response were more likely to have perpetrated IPV and had perpetrated more kinds of IPV, even when controlling for gender. These findings provide further evidence that the dorsal-ventral MPFC gradient is a critical, biological indicator of whether an individual is more or less likely to react aggressively and suggest new avenues for understanding and potentially preventing IPV perpetration.

Occupational allergic rhinitis from guar gum.

PubMed

Kanerva, L; Tupasela, O; Jolanki, R; Vaheri, E; Estlander, T; Keskinen, H

1988-05-01

Three cases of allergic rhinitis from a vegetable gum, guar gum, have been detected. Two subjects were exposed to fine guar gum powder (Emco Gum 563, Meyhall Chemical AG, Switzerland), an insulator in rubber cables, when opening cables in a power cable laboratory. After 1-2 years' exposure the patients developed rhinitis. Scratch-chamber tests, nasal provocation tests, nasal eosinophilia and a RAST test proved their allergy. A third subject developed allergic rhinitis from another guar gum product (Meyproid 5306, Meyhall Chemical AG) after 2 years' exposure in a paper factory. A positive skin test and nasal provocation test confirmed the diagnosis. A fourth case of possible allergy to guar gum after exposure to Meyproid 5306 in a paper factory is also presented. No final diagnosis was reached in this case (in 1974). The present subjects, only one of whom was atopic, developed allergy within 2 years, although their exposure to guar gum was not especially heavy. Therefore, when handling guar, adequate ventilation facilities should be provided and protective clothing, including a respiratory mask, should be worn.

Respiratory allergy to fungi in Barcelona, Spain: clinical aspects, diagnosis and specific treatment in a general allergy unit.

PubMed

Torres-Rodríguez, Josep M; Pulido-Marrero, Zeida; Vera-García, Yolanda

2012-01-01

The importance of hypersensitivity to fungal allergens is a relatively unknown and somewhat controversial subject. An open prospective study was carried out in just one centre to determine the clinical and epidemiological characteristics as well as the diagnostic usefulness of skin prick and conjunctiva provocation tests, associated with total and specific IgE determination in two groups of patients, one of which was monosensitised to fungi and the other of which had multiple sensitisations, including fungi. Rhinitis, exclusive or associated with asthma, was the main consultation cause (88% in monosensitised patients). Severe asthma was rarely found. In the polysensitised group, 64% were simultaneously allergic to moulds and mites. Alternaria alternata was the most common sensitising fungus, although a considerable number of cases were associated with other species such as Cladosporium, Penicillium and/or Aspergillus. The skin prick test gave the highest sensitivity and specificity. In 67% of the cases, the specific IgE was found between classes 3 and 4. The conjunctival provocation test was an innocuous and highly useful method for verifying the diagnosis and determining the degree of clinical sensitisation. A large number of patients exclusively allergic to fungi received specific immunotherapy, and it was generally well tolerated. This protocolised study shows the importance of Alternaria and other fungi sensitisations in rhinitis alone or associated with asthma. Combined diagnosis of prick test, specific IgE and conjunctiva provocation test is very useful for deciding specific immunotherapy. Copyright © 2011 SEICAP. Published by Elsevier Espana. All rights reserved.

Pro and Contra: Provocation Tests in Drug Hypersensitivity

PubMed Central

Soyer, Ozge; Sahiner, Umit Murat; Sekerel, Bulent Enis

2017-01-01

Drug provocation test (DPT) is the controlled administration of a drug to diagnose immune- or non-immune-mediated drug hypersensitivity and the last step for accurate recognition of drug hypersensitivity reactions when the previous diagnostic evaluations are negative or unavailable. A DPT is performed only if other conventional tests fail to yield conclusive results. In each clinical presentation, “to provoke or not to provoke” a patient should be decided after careful assessment of the risk–benefit ratio. Well-defined benefits of DPT include confirmative exclusion of diagnoses of drug hypersensitivity and provision of safe alternatives. However, disadvantages such as safety, difficulty in interpretations of results, lack of objective biomarkers, risks of resensitization, efficiency in daily practice, and lack of standardized protocols, are poorly debated. This review summarizes the current published research concerning DPT, with particular emphasis on the advantages and disadvantages of DPT in an evidence-based manner. PMID:28677662

Self-reported dietary fructose intolerance in irritable bowel syndrome: Proposed diagnostic criteria

PubMed Central

Berg, Leif Kyrre; Fagerli, Erik; Myhre, Arnt-Otto; Florholmen, Jon; Goll, Rasmus

2015-01-01

AIM: To study the criteria for self-reported dietary fructose intolerance (DFI) and to evaluate subjective global assessment (SGA) as outcome measure. METHODS: Irritable bowel syndrome (IBS) patients were randomized in an open study design with a 2 wk run-in on a habitual IBS diet, followed by 12 wk with/without additional fructose-reduced diet (FRD). Daily registrations of stool frequency and consistency, and symptoms on a visual analog scale (VAS) were performed during the first 4 wk. SGA was used for weekly registrations during the whole study period. Provocation with high-fructose diet was done at the end of the registration period. Fructose breath tests (FBTs) were performed. A total of 182 subjects performed the study according to the protocol (88 FRD, 94 controls). RESULTS: We propose a new clinically feasible diagnostic standard for self-reported fructose intolerance. The instrument is based on VAS registrations of symptom relief on FRD combined with symptom aggravation upon provocation with fructose-rich diet. Using these criteria 43 of 77 patients (56%) in the present cohort of IBS patients had self-reported DFI. To improve the concept for clinical evaluation, we translated the SGA scale instrument to Norwegian and validated it in the context of the IBS diet regimen. The validation procedures showed a sensitivity, specificity and κ value for SGA detecting the self-reported DFI group by FRD response within the IBS patients of 0.79, 0.75 and 0.53, respectively. Addition of the provocation test yielded values of 0.84, 0.76 and 0.61, respectively. The corresponding validation results for FBT were 0.57, 0.34 and -0.13, respectively. CONCLUSION: FRD improves symptoms in a subgroup of IBS patients. A diet trial followed by a provocation test evaluated by SGA can identify most responders to FRD. PMID:25987795

Reliability of provocative tests of motion sickness susceptibility

NASA Technical Reports Server (NTRS)

Calkins, D. S.; Reschke, M. F.; Kennedy, R. S.; Dunlop, W. P.

1987-01-01

Test-retest reliability values were derived from motion sickness susceptibility scores obtained from two successive exposures to each of three tests: (1) Coriolis sickness sensitivity test; (2) staircase velocity movement test; and (3) parabolic flight static chair test. The reliability of the three tests ranged from 0.70 to 0.88. Normalizing values from predictors with skewed distributions improved the reliability.

ERS technical standard on bronchial challenge testing: general considerations and performance of methacholine challenge tests.

PubMed

Coates, Allan L; Wanger, Jack; Cockcroft, Donald W; Culver, Bruce H; Diamant, Zuzana; Gauvreau, Gail; Hall, Graham L; Hallstrand, Teal S; Horvath, Ildiko; de Jongh, Frans H C; Joos, Guy; Kaminsky, David A; Laube, Beth L; Leuppi, Joerg D; Sterk, Peter J

2017-05-01

This international task force report updates general considerations for bronchial challenge testing and the performance of the methacholine challenge test. There are notable changes from prior recommendations in order to accommodate newer delivery devices. Rather than basing the test result upon a methacholine concentration (provocative concentration (PC 20 ) causing a 20% fall in forced expiratory volume in 1 s (FEV 1 )), the new recommendations base the result upon the delivered dose of methacholine causing a 20% fall in FEV 1 (provocative dose (PD 20 )). This end-point allows comparable results from different devices or protocols, thus any suitable nebuliser or dosimeter may be used, so long as the delivery characteristics are known. Inhalation may be by tidal breathing using a breath-actuated or continuous nebuliser for 1 min (or more), or by a dosimeter with a suitable breath count. Tests requiring maximal inhalations to total lung capacity are not recommended because the bronchoprotective effect of a deep breath reduces the sensitivity of the test. Copyright ©ERS 2017.

FRET-based sensors for the human M1-, M3-, and M5-acetylcholine receptors.

PubMed

Ziegler, Nicole; Bätz, Julia; Zabel, Ulrike; Lohse, Martin J; Hoffmann, Carsten

2011-02-01

Based on the recently developed approach to generate fluorescence resonance energy transfer (FRET)-based sensors to measure GPCR activation, we generated sensor constructs for the human M(1)-, M(3)-, and M(5)-acetylcholine receptor. The receptors were labeled with cyan fluorescent protein (CFP) at their C-terminus, and with fluorescein arsenical hairpin binder (FlAsH) via tetra-cysteine tags inserted in the third intracellular loop. We then measured FRET between the donor CFP and the acceptor FlAsH in living cells and real time. Agonists like acetylcholine, carbachol, or muscarine activate each receptor construct with half-maximal activation times between 60 and 70ms. Removal of the agonist caused the reversal of the signal. Compared with all other agonists, oxotremorine M differed in two major aspects: it caused significantly slower signals at M(1)- and M(5)-acetylcholine receptors and the amplitude of these signals was larger at the M(1)-acetylcholine receptor. Concentration-response curves for the agonists reveal that all agonists tested, with the mentioned exception of oxotremorine M, caused similar maximal FRET-changes as acetylcholine for the M(1)-, M(3)- and M(5)-acetylcholine receptor constructs. Taken together our data support the notion that orthosteric agonists behave similar at different muscarinic receptor subtypes but that kinetic differences can be observed for receptor activation. Copyright © 2010 Elsevier Ltd. All rights reserved.

The effects of postnatal alcohol exposure and galantamine on the context pre-exposure facilitation effect and acetylcholine efflux using in vivo microdialysis.

PubMed

Perkins, Amy E; Fadel, Jim R; Kelly, Sandra J

2015-05-01

Fetal alcohol spectrum disorders (FASD) are characterized by damage to multiple brain regions, including the hippocampus, which is involved in learning and memory. The acetylcholine neurotransmitter system provides major input to the hippocampus and is a possible target of developmental alcohol exposure. Alcohol (3.0 g/kg/day) was administered via intubation to male rat pups (postnatal day [PD] 2-10; ethanol-treated [ET]). Controls received a sham intubation (IC) or no treatment (NC). Acetylcholine efflux was measured using in vivo microdialysis (PD 32-35). ET animals were not different at baseline, but had decreased K(+)/Ca(2+)-induced acetylcholine efflux compared to NC animals and an enhanced acetylcholine response to galantamine (acetylcholinesterase inhibitor; 2.0 mg/kg) compared to both control groups. A separate cohort of animals was tested in the context pre-exposure facilitation effect task (CPFE; PD 30-32) following postnatal alcohol exposure and administration of galantamine (2.0 mg/kg; PD 11-30). Neither chronic galantamine nor postnatal alcohol exposure influenced performance in the CPFE task. Using immunohistochemistry, we found that neither alcohol exposure nor behavioral testing significantly altered the density of vesicular acetylcholine transporter or alpha7 nicotinic acetylcholine receptor in the ventral hippocampus (CA1). In the medial septum, the average number of choline acetyltransferase (ChAT+) cells was increased in ET animals that displayed the context-shock association; there were no changes in IC and NC animals that learned the context-shock association or in any animals that were in the control task that entailed no learning. Taken together, these results indicate that the hippocampal acetylcholine system is significantly disrupted under conditions of pharmacological manipulations (e.g., galantamine) in alcohol-exposed animals. Furthermore, ChAT was up‑regulated in ET animals that learned the CPFE, which may account for their ability to perform this task. In sum, developmental alcohol exposure may disrupt learning and memory in adolescence via a cholinergic mechanism. Copyright © 2015 Elsevier Inc. All rights reserved.

Manual unloading of the lumbar spine: can it identify immediate responders to mechanical traction in a low back pain population? A study of reliability and criterion referenced predictive validity

PubMed Central

Swanson, Brian T.; Riley, Sean P.; Cote, Mark P.; Leger, Robin R.; Moss, Isaac L.; Carlos,, John

2016-01-01

Background To date, no research has examined the reliability or predictive validity of manual unloading tests of the lumbar spine to identify potential responders to lumbar mechanical traction. Purpose To determine: (1) the intra and inter-rater reliability of a manual unloading test of the lumbar spine and (2) the criterion referenced predictive validity for the manual unloading test. Methods Ten volunteers with low back pain (LBP) underwent a manual unloading test to establish reliability. In a separate procedure, 30 consecutive patients with LBP (age 50·86±11·51) were assessed for pain in their most provocative standing position (visual analog scale (VAS) 49·53±25·52 mm). Patients were assessed with a manual unloading test in their most provocative position followed by a single application of intermittent mechanical traction. Post traction, pain in the provocative position was reassessed and utilized as the outcome criterion. Results The test of unloading demonstrated substantial intra and inter-rater reliability K = 1·00, P = 0·002, K = 0·737, P = 0·001, respectively. There were statistically significant within group differences for pain response following traction for patients with a positive manual unloading test (P<0·001), while patients with a negative manual unloading test did not demonstrate a statistically significant change (P>0·05). There were significant between group differences for proportion of responders to traction based on manual unloading response (P = 0·031), and manual unloading response demonstrated a moderate to strong relationship with traction response Phi = 0·443, P = 0·015. Discussion and conclusion The manual unloading test appears to be a reliable test and has a moderate to strong correlation with pain relief that exceeds minimal clinically important difference (MCID) following traction supporting the validity of this test. PMID:27559274

Dispositional anger and the resolution of the approach-avoidance conflict.

PubMed

Robinson, Michael D; Boyd, Ryan L; Persich, Michelle R

2016-09-01

The approach-avoidance conflict is one in which approaching reward brings increased threat while avoiding threat means forgoing reward. This conflict can be uniquely informative because it will be resolved in different ways depending on whether approach (toward) or avoidance (away from) is the stronger motive. Two studies (total N = 191) created a computerized version of this conflict and used the test to examine questions of motivational direction in anger. In Study 1, noise blast provocations increased the frequency of approach behaviors at high levels of trait anger, but decreased their frequency at low levels. In Study 2, a simpler version of the conflict test was used to predict anger in daily life. As hypothesized, greater approach frequencies in the test predicted greater anger reactivity to daily provocations and frustrations. The discussion focuses on the utility of the approach-avoidance conflict test and on questions of motivational direction in anger. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Bronchial provocation tests in clinical practice.

PubMed

Borges, Marcos de Carvalho; Ferraz, Erica; Vianna, Elcio Oliveira

2011-01-01

Bronchial hyperresponsiveness, which consists of an exaggerated response of the airways to bronchoconstrictor stimuli, is one of the main characteristics of asthma, presented in nearly all asthmatic patients. Bronchial hyperresponsiveness may also be present in other diseases, such as allergic rhinitis, chronic obstructive pulmonary disease, cystic fibrosis, heart failure and respiratory infection, and with some medications, such as β-blockers. Bronchial provocation tests (also known as bronchial challenges) are used to evaluate bronchial responsiveness. These tests have become increasingly used over the last 20 years, with the development and validation of accurate, safe and reproducible tests, and with the publication of well-detailed protocols. Several stimuli can be used in a bronchial challenge, and they are classified as direct and indirect stimuli. There are many indications for a bronchial challenge. In this review, we discuss the main differences between direct and indirect stimuli, and the use of bronchial challenges in clinical practice, especially for confirming diagnoses of asthma, exercise-induced bronchoconstriction and cough-variant asthma, and for use among elite-level athletes.

Attenuation in rats of impairments of memory by scopolamine, a muscarinic receptor antagonist, by mecamylamine, a nicotinic receptor antagonist.

PubMed

Newman, L A; Gold, P E

2016-03-01

Scopolamine, a muscarinic antagonist, impairs learning and memory for many tasks, supporting an important role for the cholinergic system in these cognitive functions. The findings are most often interpreted to indicate that a decrease in postsynaptic muscarinic receptor activation mediates the memory impairments. However, scopolamine also results in increased release of acetylcholine in the brain as a result of blocking presynaptic muscarinic receptors. The present experiments assess whether scopolamine-induced increases in acetylcholine release may impair memory by overstimulating postsynaptic cholinergic nicotinic receptors, i.e., by reaching the high end of a nicotinic receptor activation inverted-U dose-response function. Rats tested in a spontaneous alternation task showed dose-dependent working memory deficits with systemic injections of mecamylamine and scopolamine. When an amnestic dose of scopolamine (0.15 mg/kg) was co-administered with a subamnestic dose of mecamylamine (0.25 mg/kg), this dose of mecamylamine significantly attenuated the scopolamine-induced memory impairments. We next assessed the levels of acetylcholine release in the hippocampus in the presence of scopolamine and mecamylamine. Mecamylamine injections resulted in decreased release of acetylcholine, while scopolamine administration caused a large increase in acetylcholine release. These findings indicate that a nicotinic antagonist can attenuate impairments in memory produced by a muscarinic antagonist. The nicotinic antagonist may block excessive activation of nicotinic receptors postsynaptically or attenuate increases in acetylcholine release presynaptically. Either effect of a nicotinic antagonist-to decrease scopolamine-induced increases in acetylcholine output or to decrease postsynaptic acetylcholine receptor activation-may mediate the negative effects on memory of muscarinic antagonists.

Risk Factors for Gastrointestinal Leak after Bariatric Surgery: MBASQIP Analysis.

PubMed

Alizadeh, Reza Fazl; Li, Shiri; Inaba, Colette; Penalosa, Patrick; Hinojosa, Marcelo W; Smith, Brian R; Stamos, Michael J; Nguyen, Ninh T

2018-03-30

Gastrointestinal leak remains one of the most dreaded complications in bariatric surgery. We aimed to evaluate risk factors and the impact of common perioperative interventions on the development of leak in patients who underwent laparoscopic bariatric surgery. Using the 2015 database of accredited centers, data were analyzed for patients who underwent laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass (LRYGB). Emergent, revisional, and converted cases were excluded. Multivariate logistic regression was used to analyze risk factors for leak, including provocative testing of anastomosis, surgical drain placement, and use of postoperative swallow study. Data from 133,478 patients who underwent laparoscopic sleeve gastrectomy (n = 92,495 [69.3%]) and LRYGB (n = 40,983 [30.7%]) were analyzed. Overall leak rate was 0.7% (938 of 133,478). Factors associated with increased risk for leak were oxygen dependency (adjusted odds ratio [AOR] 1.97), hypoalbuminemia (AOR 1.66), sleep apnea (AOR 1.52), hypertension (AOR 1.36), and diabetes (AOR 1.18). Compared with LRYGB, laparoscopic sleeve gastrectomy was associated with a lower risk of leak (AOR 0.52; 95% CI 0.44 to 0.61; p < 0.01). Intraoperative provocative test was performed in 81.9% of cases and the leak rate was higher in patients with vs without a provocative test (0.8% vs 0.4%, respectively; p < 0.01). A surgical drain was placed in 24.5% of cases and the leak rate was higher in patients with vs without a surgical drain placed (1.6% vs 0.4%, respectively; p < 0.01). A swallow study was performed in 41% of cases and the leak rate was similar between patients with vs without swallow study (0.7% vs 0.7%; p = 0.50). The overall rate of gastrointestinal leak in bariatric surgery is low. Certain preoperative factors, procedural type (LRYGB), and interventions (intraoperative provocative test and surgical drain placement) were associated with a higher risk for leaks. Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Binding of quinolizidine alkaloids to nicotinic and muscarinic acetylcholine receptors.

PubMed

Schmeller, T; Sauerwein, M; Sporer, F; Wink, M; Müller, W E

1994-09-01

Fourteen quinolizidine alkaloids, isolated from Lupinus albus, L. mutabilis, and Anagyris foetida, were analyzed for their affinity for nicotinic and/or muscarinic acetylcholine receptors. Of the compounds tested, the alpha-pyridones, N-methylcytisine and cytisine, showed the highest affinities at the nicotinic receptor, while several quinolizidine alkaloid types were especially active at the muscarinic receptor.

Height velocity and IGF-I assessment in the diagnosis of childhood onset GH insufficiency: do we still need a second GH stimulation test?

PubMed

Cianfarani, Stefano; Tondinelli, Tiziana; Spadoni, Gian Luigi; Scirè, Giuseppe; Boemi, Sergio; Boscherini, Brunetto

2002-08-01

The diagnosis of GH insufficiency (GHI) in childhood is not straightforward. Our aim was to test the sensitivity and specificity of height velocity (HV), IGF-I, IGFBP-3 and GH stimulation tests alone or in combination in the diagnosis of GHI. A retrospective review of patients with GHI and idiopathic short stature (ISS) diagnosed in our centre and followed up to the completion of linear growth. Thirty-three GHI children and 56 children with ISS were evaluated. GHI diagnosis was based on fulfilment of anthropometric, endocrine and neuroradiological criteria: stature < or = -2 z-score, delayed bone age (at least 1 year), GH peak response to at least two different provocative tests < 10 micro g/l (20 mU/l), brain MRI positive for hypothalamus-pituitary abnormalities, catch-up growth during the first year of GH replacement therapy > or = 75th centile, peak GH response to a third provocative test after growth completion < 10 micro g/l (20 mU/l). Children with anthropometry resembling that of GHI but with peak GH responses > 10 micro g/l (20 mU/l) were diagnosed as ISS. All subjects underwent standard anthropometry. GH secretory status was assessed by clonidine, arginine and GHRH plus arginine stimulation tests. IGF-I and IGFBP-3 circulating levels were measured by immunoradiometric assay (IRMA). The following cut-off values were chosen to discriminate between GHI and nonGHI short children: HV < 25th centile over the 6-12 months prior to the initiation of GH therapy, peak GH responses < 10 or < 7 micro g/l (< 20 or < 14 mU/l) and IGF-I and IGFBP-3-values < -1.9 z-score. Sensitivity (true positive ratio) and specificity (true negative ratio) were evaluated. Taking 10 micro g/l (20 mU/l) as the cut-off value, sensitivity was 100% and specificity 57% for GH provocative tests, whereas taking 7 as the cut-off value, sensitivity was 66% and specificity rose to 78%. Sensitivity was 73% for IGF-I and 30% for IGFBP-3 measurement, whilst specificity was 95% for IGF-I and 98% for IGFBP-3 evaluation. HV assessment revealed a sensitivity of 82% and a specificity of 43%. When HV and IGF-I evaluations were used in combination, sensitivity reached 95% and specificity 96%. When both HV and IGF-I are normal (26% of our subjects) GHI may be ruled out, whereas when both the indices are subnormal (23%) GHI is so highly likely that the child may undergo only one GH provocative test and brain MRI and, thereafter, may begin GH therapy without any further test. In case of discrepancy, when IGF-I is normal and HV < 25th centile (44% of children), due to the relatively low sensitivity of IGF-I assessment and low specificity of HV, the patient should undergo GH tests and brain MRI. Finally, in the rare case of HV > 25th centile and subnormal IGF-I-values (7%), due to the high specificity of IGF-I measurement, the child should undergo one provocative test and brain MRI for the high suspicion of GHI. Our results suggest that a simple assessment of HV and basal IGF-I may exclude or, in association with only one stimulation test, confirm the diagnosis of GH insufficiency in more than half of patients with short stature.

Collateral Damage: How High-Stakes Testing Corrupts America's Schools

ERIC Educational Resources Information Center

Nichols, Sharon L.; Berliner, David C.

2007-01-01

Drawing on their extensive research, Nichols and Berliner document and categorize the ways that high-stakes testing threatens the purposes and ideals of the American education system. For more than a decade, the debate over high-stakes testing has dominated the field of education. This passionate and provocative book provides a fresh perspective…

Ergonovine-induced changes of coronary artery diameter in patients with nonsignificant coronary artery stenosis : relation with lipid profile.

PubMed

Nedeljkovic, Milan A; Ostojic, Miodrag C; Beleslin, Branko D; Nedeljkovic, Ivana; Milic, Natasa; Vukcevic, Vladan; Stojkovic, Sinisa; Saponjski, Jovica; Orlic, Dejan; Djordjevic-Dikic, Ana; Stepanovic, Jelena; Giga, Vojislav; Petrasinovic, Zorica; Arandjelovic, Aleksandra; Beleslin, Biljana; Kanjuh, Vladimir

2007-06-01

Serum cholesterol is positively associated with the risk of developing coronary heart disease. The aim of this study was to determine the relation between response of coronary arteries to ergonovine provocation and lipid profile in patients with nonsignificant coronary artery disease. 105 patients (46 male, 59 female, mean age 52 +/- 8 years) with chest pain syndrome and nonsignificant coronary artery stenosis (< 50% diameter stenosis) were analyzed. Ergonovine test was performed at the end of diagnostic catheterization. Coronary spasm was defined as total or near total obstruction of the coronary artery. By quantitative coronary arteriography, changes of minimal luminal diameter (MLD) during ergonovine provocation were evaluated. Total cholesterol, LDL and HDL cholesterol, and triglycerides were measured. There was a significant negative correlation between resting MLD and LDL cholesterol (r = -0.215; p = 0.034), and a significant positive correlation between MLD decrease provoked by ergonovine and total cholesterol (r = 0.275; p = 0.006), as well as LDL cholesterol (r = 0.284; p = 0.004), but not for HDL cholesterol and triglycerides (p = NS [not significant]). In patients with nonsignificant coronary artery stenosis evaluated by ergonovine provocation, there was not only a significant negative correlation between MLD and LDL cholesterol, but also a positive correlation between coronary vasoconstriction induced by ergonovine provocation and both total and LDL cholesterol.

Bite by a dog under provocation: is it free from risk?

PubMed

Dutta, J K

2002-05-01

There is a common belief that rabid dogs bite without provocation, hence a dog bite under provocation is free from the risk of rabies. This is not always true as is evident from the case report narrated below. Here in this article, a man of 38 years was bitten by a dog under provocation. He developed rabies 4 months after the bite and subsequently died. Autopsy revealed Negri bodies from the brain tissue.

Increased plasma xanthine oxidoreductase activity deteriorates coronary artery spasm.

PubMed

Watanabe, Ken; Shishido, Tetsuro; Otaki, Yoichiro; Watanabe, Tetsu; Sugai, Takayuki; Toshima, Taku; Takahashi, Tetsuya; Yokoyama, Miyuki; Kinoshita, Daisuke; Murase, Takayo; Nakamura, Takashi; Wanezaki, Masahiro; Tamura, Harutoshi; Nishiyama, Satoshi; Takahashi, Hiroki; Arimoto, Takanori; Yamauchi, So; Yamanaka, Tamon; Miyamoto, Takuya; Kubota, Isao; Watanabe, Masafumi

2018-06-23

Increased reactive oxygen species (ROS) contributes to the development of endothelial dysfunction, which is involved in coronary artery spasm (CAS). Xanthine oxidoreductase (XOR) plays a pivotal role in producing both uric acid and ROS. However, the association between plasma XOR activity and CAS has not been elucidated. The aim of this study was to investigate whether plasma XOR activity is associated with CAS. We measured XOR activity in 104 patients suspected for CAS, who presented without significant coronary artery stenosis and underwent intracoronary acetylcholine provocation tests. CAS was provoked in 44 patients and they had significantly higher XOR activity as compared with those without CAS. The patients were divided into three groups based on the XOR activity. The prevalence rate of CAS was increased with increasing XOR activity. A multivariate logistic regression analysis showed that the 3rd tertile group exhibited a higher incidence of CAS as compared with the 1st tertile group [odds ratio (OR) 6.9, P = 0.001) and the 2nd tertile group (OR 3.2, P = 0.033) after adjustment for conventional CAS risk factors, respectively. The C index was significantly improved by the addition of XOR activity to the baseline model based on CAS risk factors. Furthermore, the 3rd tertile group had the highest incidence of severe spasm defined as total obstruction, flow-limiting stenosis, diffuse spasm, multivessel spasm, and/or lethal arrhythmia. This is a first report to elucidate the association of plasma XOR activity with CAS. Increased plasma XOR activity is significantly associated with CAS.

Provocative questions in cancer epidemiology in a time of scientific innovation and budgetary constraints.

PubMed

Lam, Tram Kim; Schully, Sheri D; Rogers, Scott D; Benkeser, Rachel; Reid, Britt; Khoury, Muin J

2013-04-01

In a time of scientific and technological developments and budgetary constraints, the National Cancer Institute's (NCI) Provocative Questions Project offers a novel funding mechanism for cancer epidemiologists. We reviewed the purposes underlying the Provocative Questions Project, present information on the contributions of epidemiologic research to the current Provocative Questions portfolio, and outline opportunities that the cancer epidemiology community might capitalize on to advance a research agenda that spans a translational continuum from scientific discoveries to population health impact.

Occupational formalin asthma.

PubMed Central

Hendrick, D J; Lane, D J

1977-01-01

Hypersensitivity to formalin used to sterilise artificial kidney machines was shown by inhalation provocation tests to be responsible for attacks of wheezing accompanied by productive cough in two members of the nursing staff of a haemodialysis unit. Three further members of the staff of 28 who were continually exposed to this substance occupationally had developed similar recurrent but less frequent episodes since joining the unit. Two underwent inhalation provocation tests with formalin which did not reproduce these symptoms.Single episodes of these symptoms had been noted by three additional staff members so that altogether eight (29%) had experienced attacks described as bronchitic since becoming exposed to formalin. We suggest that, while exposure to formalin did not seem to be directly responsible in all cases, it might have increased susceptibility to other provoking agents or induced a hyper-reactive responsiveness of the airways. The responses observed in the two nurses after inhalation provocation tests with fromalin were predominantly of airways obstruction. Wheezing began between two and three hours after exposure, and peak expiratory flow rates fell maximally by approximately 50%. Reactions persisted for 10 hours to 10 days depending on the exposure dose. A productive cough was a prominent feature. The sputum appeared to be mucopurulent, but culture produced a scanty growth of Haemophilus influenzae only, together with upper respiratory tract commensals. The cellular content was not homogeneous, neutrophil leucocytes and eosinophil leucocoytes variably dominating. Variable responses of neutrophil and eosinophil leucocytes were also seen in the peripheral blood. PMID:557329

Cold-provocation testing for the vascular component of hand-arm vibration syndrome in health surveillance.

PubMed

Poole, Kerry; Elms, Joanne; Mason, Howard

2006-10-01

The aim was to investigate whether the use of infra-red thermography (I-R) and measurement of temperature gradients along the finger could improve the diagnostic accuracy of cold-provocation testing (15 degrees C for 5 min) in vascular hand-arm vibration syndrome (HAVS). Twenty-one controls and 33 individuals with stages 2/3V HAVS were studied. The standard measurement of time to rewarm by 4 degrees C (T4 degrees C) and temperature gradients between the finger tip, base and middle (measured using I-R) were calculated. Receiver Operating Characteristics (ROC) analysis to distinguish between the two groups revealed that for T4 degrees C the area under the ROC curve was not statistically significantly different from 0.5 (0.64 95% confidence interval 0.49-0.76). The difference between the tip and middle portion of the finger during the sixth minute of recovery was the most promising gradient with an area of 0.76 (95% confidence interval 0.62-0.87), and sensitivity and specificity of 57.6% and 85.7% respectively. However, this was not significantly different from that for the time to rewarm by 4 degrees C. In conclusion, the cold-provocation test used in this study does not appear to discriminate between individuals with stage 2/3V HAVS and controls and this is not improved by the measurement of temperature gradients along the fingers using I-R.

Distilled water nasal provocation in hyperreactive patients.

PubMed

Baudoin, T; Anzic, S A; Kalogjera, L

1999-01-01

Nonisotonic aerosol may act as a provocation agent in the upper and lower airways of hyperreactive individuals. The purpose of the study was to compare the results of nasal challenge with distilled water in patients with allergic rhinitis to those with noninfective nonallergic rhinitis (NINAR), with respect to the potential clinical use of the obtained data. A group of 68 ambulatory patients with allergic rhinitis or NINAR (39 perennial allergic, 6 seasonal, 23 NINAR) were challenged with 10 mL of distilled water aerosol after the baseline active anterior rhinomanometry. Patients with nasal polyposis at endoscopy, significant unilateral septal deviation, positive bacteriologic swab, recent nasal surgery, and uncertain anamnestic data about the medication taken 6 weeks before the provocation were excluded from the study. After 10 minutes of nasal provocation, rhinomanometry was repeated to assess the response. In 15 patients of the perennial allergic group, the same measurements were performed after a 2-week oral antihistamine and topical steroid therapy. Nasal resistance was significantly increased on the more patent side of the nose after nasal provocation with distilled water aerosol in allergic patients in comparison to the nasal resistance before provocation. In the patients with NINAR, the provocation resulted in a significant rise on the more patent side, but the total nasal airway resistance (NAR) levels were also significantly increased. The systemic antihistamine and topical steroid 2-week therapy in patients with perennial allergic rhinitis significantly reduced the response to nasal distilled water provocation. Nasal provocation with distilled water aerosol is a cheap, simple, and acceptable method that provides useful clinical data on the level of nonspecific nasal hyperreactivity and the therapy success.

Some enzymatic properties of brain Acetylcholinesterase from bluegill and channel catfish

USGS Publications Warehouse

Hogan, James W.; Knowles, Charles O.

1968-01-01

Using a manometric technique an acetylcholinesterase (EC 3.1.1.7, acetylcholine acetyl-hydrolase) was demonstrated in brain tissue from the bluegill, Lepomis macrochirus Rafinesque, and the channel catfish, Ictalurus punctatus (Walbaum). The activities were 19 and 37 μmoles acetylcholine hydrolyzed/milligram protein per hour for the bluegill and channel catfish enzymes, respectively. The optimum substrate concentration for the hydrolysis of acetylcholine was 10 mMfor the enzymes from both species. Generally, the catfish acetylcholinesterase was somewhat more susceptible than the bluegill to the inhibitors tested; however, the bluegill enzyme was more susceptible to inhibition by malathion and malaoxon.

Attenuation in rats of impairments of memory by scopolamine, a muscarinic receptor antagonist, by mecamylamine, a nicotinic receptor antagonist

PubMed Central

Newman, L. A.

2015-01-01

Rationale Scopolamine, a muscarinic antagonist, impairs learning and memory for many tasks, supporting an important role for the cholinergic system in these cognitive functions. The findings are most often interpreted to indicate that a decrease in postsynaptic muscarinic receptor activation mediates the memory impairments. However, scopolamine also results in increased release of acetylcholine in the brain as a result of blocking presynaptic muscarinic receptors. Objectives The present experiments assess whether scopolamine-induced increases in acetylcholine release may impair memory by overstimulating postsynaptic cholinergic nicotinic receptors, i.e., by reaching the high end of a nicotinic receptor activation inverted-U dose-response function. Results Rats tested in a spontaneous alternation task showed dose-dependent working memory deficits with systemic injections of mecamylamine and scopolamine. When an amnestic dose of scopolamine (0.15 mg/kg) was co-administered with a subamnestic dose of mecamylamine (0.25 mg/kg), this dose of mecamylamine significantly attenuated the scopolamine-induced memory impairments. We next assessed the levels of acetylcholine release in the hippocampus in the presence of scopolamine and mecamylamine. Mecamylamine injections resulted in decreased release of acetylcholine, while scopolamine administration caused a large increase in acetylcholine release. Conclusions These findings indicate that a nicotinic antagonist can attenuate impairments in memory produced by a muscarinic antagonist. The nicotinic antagonist may block excessive activation of nicotinic receptors postsynaptically or attenuate increases in acetylcholine release presynaptically. Either effect of a nicotinic antagonist—to decrease scopolamine-induced increases in acetylcholine output or to decrease post-synaptic acetylcholine receptor activation—may mediate the negative effects on memory of muscarinic antagonists. PMID:26660295

Angular velocities, angular accelerations, and coriolis accelerations

NASA Technical Reports Server (NTRS)

Graybiel, A.

1975-01-01

Weightlessness, rotating environment, and mathematical analysis of Coriolis acceleration is described for man's biological effective force environments. Effects on the vestibular system are summarized, including the end organs, functional neurology, and input-output relations. Ground-based studies in preparation for space missions are examined, including functional tests, provocative tests, adaptive capacity tests, simulation studies, and antimotion sickness.

The object of my aggression: Sexual objectification increases physical aggression toward women.

PubMed

Vasquez, Eduardo A; Ball, Louisa; Loughnan, Steve; Pina, Afroditi

2018-01-01

Objectification involves reducing someone to a sexual object, rather than seeing them as a full person. Despite numerous theoretical claims that people are more aggressive toward the objectified, and empirical evidence that objectification is linked to high willingness to aggress, rape proclivity, and aggressive attitudes, no research has examined a causal link between objectification and physical aggression, particularly in the context of provocation. In two experiments, we examined this predicted link. In Experiment 1, using a 2 (objectification: no/yes) × 2 (provocation: no/yes) factorial between-subjects design, we investigated the effects of objectification, induced via body focus during a face-to-face interaction, and provocation on physical aggression toward a female confederate. Our results revealed a significant main effect of provocation, a marginal main effect of objectification, and a significant interaction between these variables. In the absence of a provocation, focusing on a woman's body increased aggression toward her. Experiment 2 replicated Experiment 1 using a video of a target woman instead of a face-to-face interaction. Again, our results showed a significant two-way interaction between objectification and provocation, wherein objectification increased aggression in the absence of provocation. Overall, this research indicates that objectification can lead to heightened physical aggression toward objectified women. © 2017 Wiley Periodicals, Inc.

Sensitivity to tomato and peanut allergens in children monosensitized to grass pollen.

PubMed

de Martino, M; Novembre, E; Cozza, G; de Marco, A; Bonazza, P; Vierucci, A

1988-04-01

Possible associations between allergy to grass pollen and positive skin tests to food allergens were studied in 102 children monosensitized (as to inhalant allergens) to grass pollen, and in 117 children monosensitized (as to inhalant allergens) to Dermatophagoides. Thirty-two foods were tested by an epicutaneous method. Positive skin tests to food allergens were more frequent in children with allergy to grass pollen (59.8%) than in children with allergy to Dermatophagoides (9.4%). A considerably high frequency of positive reactions to tomato (39.2%), peanut (22,5%), green pea (13.7%), and wheat (11.7%) was observed in children with allergy to grass pollen. Positive skin tests to peanut closely correlated with positive RAST results and nasal provocation tests, whereas in children with skin test positivity to tomato a close correlation with nasal provocation tests but a 45% correlation with a positive RAST result were observed. RAST inhibition experiments were carried out, and the results may suggest the presence of cross-reacting IgE to grass pollen, tomato, and peanut antigens. Clinical implications of these findings are discussed in the light of histories of food hypersensitivity, urticaria-angioedema, and atopic dermatitis in children with allergy to grass pollen.

Nonimmediate hypersensitivity reactions to iodinated contrast media.

PubMed

Gómez, Enrique; Ariza, Adriana; Blanca-López, Natalia; Torres, Maria J

2013-08-01

To provide a detailed analysis of the latest findings on the mechanisms underlying the nonimmediate reactions to iodinated contrast media and comment on the recent advances in diagnosis, focusing on the roles of the skin test, drug provocation test (DPT), and lymphocyte transformation test (LTT). Several studies have reported new findings supporting an important role for T-lymphocytes in the nonimmediate reactions to iodinated contrast media. The LTT has been used as an in-vitro tool for diagnosis, but with variable results. However, the inclusion of autologous monocyte-derived dendritic cells as professional antigen-presenting cells has improved the sensitivity of this test. Regarding in-vivo diagnosis, although skin testing has been routine, it has now been shown that its sensitivity and negative predictive value are low. Recent studies have demonstrated that the DPT is a well tolerated and useful procedure that is necessary to confirm the diagnosis of nonimmediate hypersensitivity reactions to iodinated contrast media. Nonimmediate reactions to contrast media are usually T-cell mediated. Diagnosis is based on skin testing, although its sensitivity and negative predictive value are not optimal. Consequently, drug provocation testing is often needed to confirm the diagnosis and also to seek alternative contrast media that can be tolerated.

Provocation of Symmetry/Ordering Symptoms in Anorexia nervosa: A Functional Neuroimaging Study

PubMed Central

Giampietro, Vincent; Uher, Rudolf; Mataix-Cols, David; Brammer, Michael J.; Williams, Steven C. R.; Treasure, Janet; Campbell, Iain C.

2014-01-01

Anorexia nervosa (AN), obsessive–compulsive disorder (OCD), and obsessive–compulsive personality disorder (OCPD) are often co-morbid; however, the aetiology of such co-morbidity has not been well investigated. This study examined brain activation in women with AN and in healthy control (HC) women during the provocation of symmetry/ordering-related anxiety. During provocation, patients with AN showed more anxiety compared to HCs, which was correlated with the severity of symmetry/ordering symptoms. Activation in the right parietal lobe and right prefrontal cortex (rPFC) in response to provocation was reduced in the AN group compared with the HC group. The reduced right parietal activation observed in the AN group is consistent with parietal lobe involvement in visuospatial cognition and with studies of OCD reporting an association between structural abnormalities in this region and the severity of ‘ordering’ symptoms. Reduced rPFC activation in response to symmetry/ordering provocation has similarities with some, but not all, data collected from patients with AN who were exposed to images of food and bodies. Furthermore, the combination of data from the AN and HC groups showed that rPFC activation during symptom provocation was inversely correlated with the severity of symmetry/ordering symptoms. These data suggest that individuals with AN have a diminished ability to cognitively deal with illness-associated symptoms of provocation. Furthermore, our data also suggest that symptom provocation can progressively overload attempts by the rPFC to exert cognitive control. These findings are discussed in the context of the current neurobiological models of AN. PMID:24844926

Provocation of symmetry/ordering symptoms in Anorexia nervosa: a functional neuroimaging study.

PubMed

Suda, Masashi; Brooks, Samantha J; Giampietro, Vincent; Uher, Rudolf; Mataix-Cols, David; Brammer, Michael J; Williams, Steven C R; Treasure, Janet; Campbell, Iain C

2014-01-01

Anorexia nervosa (AN), obsessive-compulsive disorder (OCD), and obsessive-compulsive personality disorder (OCPD) are often co-morbid; however, the aetiology of such co-morbidity has not been well investigated. This study examined brain activation in women with AN and in healthy control (HC) women during the provocation of symmetry/ordering-related anxiety. During provocation, patients with AN showed more anxiety compared to HCs, which was correlated with the severity of symmetry/ordering symptoms. Activation in the right parietal lobe and right prefrontal cortex (rPFC) in response to provocation was reduced in the AN group compared with the HC group. The reduced right parietal activation observed in the AN group is consistent with parietal lobe involvement in visuospatial cognition and with studies of OCD reporting an association between structural abnormalities in this region and the severity of 'ordering' symptoms. Reduced rPFC activation in response to symmetry/ordering provocation has similarities with some, but not all, data collected from patients with AN who were exposed to images of food and bodies. Furthermore, the combination of data from the AN and HC groups showed that rPFC activation during symptom provocation was inversely correlated with the severity of symmetry/ordering symptoms. These data suggest that individuals with AN have a diminished ability to cognitively deal with illness-associated symptoms of provocation. Furthermore, our data also suggest that symptom provocation can progressively overload attempts by the rPFC to exert cognitive control. These findings are discussed in the context of the current neurobiological models of AN.

Hemodynamic changes in systolic and diastolic function during isoproterenol challenge predicts symptomatic response to myectomy in hypertrophic cardiomyopathy with labile obstruction.

PubMed

Prasad, Megha; Geske, Jeffrey B; Sorajja, Paul; Ommen, Steve R; Schaff, Hartzell V; Gersh, Bernard J; Nishimura, Rick A

2016-11-15

We aimed to assess the utility of changes in systolic and diastolic function by isoproterenol challenge in predicting symptom resolution post-myectomy in selected patients with hypertrophic cardiomyopathy (HCM) and labile obstruction. In a subset of symptomatic HCM patients without resting/provocable obstruction on noninvasive assessment, isoproterenol challenge during hemodynamic catheterization may elicit labile left ventricular outflow tract (LVOT) obstruction, and demonstrate the effect of obstruction on diastolic function. These changes may determine whether patients achieve complete symptom resolution post-myectomy. Between February 2003 and April 2009, 18 symptomatic HCM patients without LVOT obstruction on noninvasive testing underwent isoproterenol provocation and septal myectomy due to presence of provocable gradient and were followed for 4 (IQR 3-7) years. Thirteen (72.2%) had complete symptom resolution, while 5 (27.8%) had improved, but persistent symptoms. Those with provoked gradient >100 mm Hg or increase in left atrial pressure (LAP) with isoproterenol had symptom resolution. Symptomatic HCM patients without LVOT gradient on noninvasive testing may demonstrate labile obstruction with isoproterenol. With isoproterenol, patients with high LVOT gradient or increase in LAP concomitant with an increase in gradient achieved complete symptom resolution post-myectomy. Thus, improved diastolic filling as well as outflow gradient production in patients with HCM may predict symptom response to myectomy. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Gender Differences in Intended Escalatory Tendencies among Marital Partners

ERIC Educational Resources Information Center

Winstok, Zeev; Straus, Murray A.

2011-01-01

This study addresses the intended escalatory tendency in eight hypothetical situations in which the provocator's identity (partner or stranger, male or female) and the provocation form (verbal or physical aggression) were manipulated. The research question is "how does the identity of the provocator and the form of his or her provocation…

The Power of the Provocative: Exploring World History Content

ERIC Educational Resources Information Center

Ashkettle, Bryan L.

2013-01-01

This study addresses how my freshman world history students come to understand controversial issues as provocative within the secondary social studies classroom, and in what ways does their engagement with provocative issues influence their understanding of the content and the world around them. In addition, this research study seeks to discover…

Rational ideation and empiric validation of an innovative digital dermographic tester.

PubMed

Lembo, C; Patruno, C; Balato, N; Ayala, F; Balato, A; Lembo, S

2018-04-01

Dermographism is a condition characterized by a weal response to a combination of pressure and traction on skin surface, and its diagnosis is based on medical history, clinical criteria and provocation test. The Dermographic Tester ® , a pen-sized tool containing a spring-loaded blunt tip, is the most widely used instrument for the provocation test, and it exerts increasing pressures on the skin surface according to an arbitrary units (AU) scale. Analysing the mechanism of function and trying to convert the AUs to SI units (g/mm 2 ), we found that this instrument had some defects and limits that would compromise a true and repeatable quantification of the weal response threshold. Consequently, we decided to develop a new instrument, the Digital Dermographic Tester (DDT), which is engineered with an inside force sensor to implement features lacking in the current tools, in the hope of enhancing the precision of the provocation test. To validate the effectiveness and accuracy of the DDT. We tested the DDT on 213 participants purposely sampled to obtain three groups, each with a different pattern of reaction to mechanical stimuli. Based on anamnestic, diagnostic and symptomatic criteria, patients were divided into dermographic urticaria (DU), spontaneous urticaria (SU) and healthy control (HC) groups. The DDT was used to apply 12 levels of pressure to the skin surface, and a frequency distribution of positive reactions was displayed for each group. A force of 36-40 g/mm 2 appropriately differentiated physiological from pathological conditions with high sensitivity and specificity. The DDT was found to be capable of differentiating patients with DU patients from those with SU and from HCs, and was able to precisely identify the weal elicitation threshold. © 2017 British Association of Dermatologists.

Cardiovascular and cortisol reactivity and habituation to a virtual reality version of the Trier Social Stress Test: a pilot study.

PubMed

Jönsson, Peter; Wallergård, Mattias; Osterberg, Kai; Hansen, Ase Marie; Johansson, Gerd; Karlson, Björn

2010-10-01

The Trier Social Stress Test (TSST) is a widely used protocol to induce stress in laboratory settings. Briefly, in the TSST, the test participant is asked to hold a speech and to do an arithmetic task in front of an audience. In the present pilot study, we examined endocrine and autonomic reactivity and habituation to repeated stress provocations using a virtual reality (VR) version of TSST. The VR system was a CAVE™ system with three rear projected walls (4 m×3 m), and one floor projection. The system also included a head tracking system and passive stereoscopy. The virtual audience consisted of one woman, and two men. Ten healthy men, mean age 28.3 years (24-38 years), were confronted with the test twice (1 week between sessions), during which salivary cortisol, heart rate (HR), high frequency heart rate variability (HF-HRV, parasympathetic activity), and T-wave amplitude (TWA, suggested to be related to sympathetic influence on myocardial performance) were assessed. Cortisol secretion showed a marked increase (88% vs. baseline) during the first stress provocation, but habituated in the second session. The magnitude of HR and TWA reactivity during stress provocation was approximately the same at both sessions, implying a stable increase in sympathetic activity. Heart rate showed a maximum increase of 40% at the first session, and 32% at the second. TWA showed a maximum decrease of 42% at the first session, and 39% at the second. The results resemble those obtained in prior studies using the real-life TSST. If these results can be replicated with larger samples, VR technology may be used as a simple and standardized tool for social stress induction in experimental settings. Copyright © 2010 Elsevier Ltd. All rights reserved.

Adenosine bronchial provocation with computerized wheeze detection in young infants with prolonged cough: correlation with long-term follow-up.

PubMed

Bentur, Lea; Beck, Raphael; Berkowitz, Drora; Hasanin, Jamal; Berger, Irit; Elias, Nael; Gavriely, Noam

2004-10-01

Chronic cough in babies is often associated with bronchial hyperreactivity (BHR). The objective documentation of BHR in babies is difficult, and acoustic methods have been described (provocative concentration of a substance causing wheeze) for conducting bronchial provocation tests (BPTs). We conducted a study to evaluate automatic computerized wheeze detection (CWD) in determining BHR in young infants with prolonged cough, and its correlation with the subsequent development of wheezing. Infants aged < 24 months with prolonged cough (ie, > 2 months) underwent acoustic BPTs with the response determined by CWD and auscultation by a physician. Telephone interviews with parents were conducted after 1 month and yearly for the next 3 years. A total of 28 infants who were 4 to 24 months old with prolonged cough were included in the study. Twenty of these infants (71.4%) had BHR as determined by a positive acoustic BPT result. In 11 of these 20 tests, the CWD occurred earlier, and in 9 tests it occurred at the same step as auscultation by a physician. Rhonchi or whistles often preceded wheezes. Seventeen of the 20 patients with BHR completed 3 years of follow-up. Of these, 14 had recurrent episodes of wheezing and shortness of breath, and 3 were well. Six of the eight adenosine-negative patients completed 3 years of follow-up and had no symptoms of BHR. Acoustic BPT is a technically feasible test for the detection of BHR in young infants. CWD provides an earlier detection of wheeze than stethoscope auscultation. In our group of infants, a positive acoustic BPT result had high correlation with symptoms compatible with BHR over the next 3 years.

Pain referral and regional deep tissue hyperalgesia in experimental human hip pain models.

PubMed

Izumi, Masashi; Petersen, Kristian Kjær; Arendt-Nielsen, Lars; Graven-Nielsen, Thomas

2014-04-01

Hip disorder patients typically present with extensive pain referral and hyperalgesia. To better understand underlying mechanisms, an experimental hip pain model was established in which pain referrals and hyperalgesia could be studied under standardized conditions. In 16 healthy subjects, pain was induced by hypertonic saline injection into the gluteus medius tendon (GMT), adductor longus tendon (ALT), or gluteus medius muscle (GMM). Isotonic saline was injected contralaterally as control. Pain intensity was assessed on a visual analogue scale (VAS), and subjects mapped the pain distribution. Before, during, and after injections, passive hip joint pain provocation tests were completed, together with quantitative sensory testing as follows: pressure pain thresholds (PPTs), cuff algometry pain thresholds (cuff PPTs), cutaneous pin-prick sensitivity, and thermal pain thresholds. Hypertonic saline injected into the GMT resulted in higher VAS scores than hypertonic injections into the ALT and GMM (P<.05). Referred pain areas spread to larger parts of the leg after GMT and GMM injections compared with more regionalized pain pattern after ALT injections (P<.05). PPTs at the injection site were decreased after hypertonic saline injections into GMT and GMM compared with baseline, ALT injections, and isotonic saline. Cuff PPTs from the thigh were decreased after hypertonic saline injections into the ALT compared with baseline, GMT injections, and isotonic saline (P<.05). More subjects had positive joint pain provocation tests after hypertonic compared with isotonic saline injections (P<.05), indicating that this provocation test also assessed hyperalgesia in extra-articular soft tissues. The experimental models may open for better understanding of pain mechanisms associated with painful hip disorders. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Diagnosis of mold allergy by RAST and skin prick testing.

PubMed

Nordvall, S L; Agrell, B; Malling, H J; Dreborg, S

1990-11-01

Sera from 33 patients with mold allergy proven by bronchial provocation were analyzed for specific IgE against six mold species comparing an improved Phadebas RAST with four other techniques. The new method was more sensitive and gave significantly higher IgE antibody concentrations for all tested molds except Cladosporium herbarum.

Standardization of motion sickness induced by left-right and up-down reversing prisms

NASA Technical Reports Server (NTRS)

Reschke, M. F.; Vanderploeg, J. M.; Brumley, E. A.; Kolafa, J. J.; Wood, S. J.

1990-01-01

Reversing prisms are known to produce symptoms of motion sickness, and have been used to provide a chronic stimulus for training subjects on symptom recognition and regulation. However, testing procedures with reversing prisms have not been standardized. A set of procedures were evaluated which could be standardized using prisms for provocation and to compare the results between Right/Left Reversing Prisms (R/L-RP) and Up/Down Reversing Prisms (U/D-RP). Fifteen subjects were tested with both types of prisms using a self paced walking course throughout the laboratory with work stations established at specified intervals. The work stations provided tasks requiring eye-hand-foot coordination and various head movements. Comparisons were also made between these prism tests and two other standardized susceptibility tests, the KC-135 parabolic static chair test and the Staircase Velocity Motion Test (SVMT). Two different types of subjective symptom reports were compared. The R/L-RP were significantly more provocative than the U/D-RP. The incidence of motion sickness symptoms for the R/L-RP was similar to the KC-135 parabolic static chair test. Poor correlations were found between the prism tests and the other standardized susceptibility tests, which might indicate that different mechanisms are involved in provoking motion sickness for these different tests.

Painful and provocative events scale and fearlessness about death among Veterans: Exploratory factor analysis.

PubMed

Poindexter, Erin K; Nazem, Sarra; Forster, Jeri E

2017-01-15

The interpersonal theory of suicide suggests three proximal risk factors for suicide: perceived burdensomeness, thwarted belongingness, and acquired capability. Previous literature indicates that repetitive exposure to painful and provocative events is related to increased acquired capability for suicide. Despite this, research related to the assessment of painful and provocative events has been insufficient. Research has inconsistently administered the Painful and Provocative Events Scale (PPES; a painful and provocative events assessment), and no study has examined the factor structure of the English PPES. This study explored the factor structure of the PPES and the relation between factors and fearlessness about death. The sample was a cross-sectional, self-report study comprised of 119 Veterans (Mage = 46.5, SD = 13.5). Findings from an exploratory factor analysis indicated a four-factor solution for the PPES; however, no factor from the PPES significantly related to fearlessness about death (measured by the Acquired Capability for Suicide Scale - Fearlessness About Death Scale; all p >.21). Cross-sectional, small Veteran sample. Findings suggest that the PPES lacks the psychometric properties necessary to reliably investigate painful and provocative factors. Consequently, this measure may not reliably capture and explain how painful and provocative events relate to fearlessness about death, which is a barrier to improving suicide risk assessment and prediction. Recommendations for the construction of a new PPES are offered. Published by Elsevier B.V.

North Korea’s Choice of the Types of Provocation Against South Korea

DTIC Science & Technology

2013-12-01

DISTRIBUTION CODE A 13. ABSTRACT (maximum 200 words) This research starts from the question of how North Korea decides upon the types of its provocations...INTENTIONALLY LEFT BLANK iv ABSTRACT This research starts from the question of how North Korea decides upon the types of its provocations...1 A. MAJOR RESEARCH QUESTION................................................................1 B

The diagnostic value of finger systolic blood pressure and cold-provocation testing for the vascular component of hand-arm vibration syndrome in health surveillance.

PubMed

Poole, K; Elms, J; Mason, H J

2004-12-01

Hand-arm vibration syndrome (HAVS) is a complex condition with vascular, sensorineural and musculoskeletal components. A number of quantitative tests have been used for assisting in the diagnosis of HAVS and grading disease severity. To investigate and compare the diagnostic value of finger systolic blood pressure (FSBP) and rewarming of finger skin temperature (FST) following cold-provocation testing, in the assessment of vascular HAVS. Twenty-four individuals with vascular HAVS (Stockholm Workshop stage 2 or 3V) and 22 control subjects underwent FSBP measurements at 30, 15 and 10 degrees C and monitoring of FST following immersion of the hands in water at 15 degrees C for 5 min. There was a significant reduction in median FSBP% in the vascular HAVS group in the change in FSBP from 30 to 15 degrees C adjusted for brachial blood pressure (FSBPC%). There was no difference in the median time for FST to rewarm by 4 degrees C between HAVS cases and controls. The sensitivity and specificity of FSBP to discriminate between the groups varied between 44 and 61% and 91 and 95%, respectively. The sensitivity and specificity for the time for FST to rewarm by 4 degrees C were 71 and 77%. There is little evidence that the described form of finger rewarming after cold-provocation testing is a useful diagnostic test for vascular HAVS, although it may have some moderate influence in ruling out vascular problems. Based on our data, the FSBP may also have limited use in confirming a positive diagnosis of vibration-induced vascular problems. The higher specificity of the FSBP test suggests it may have some value in ruling out the vascular component of HAVS. The data from this study do not confirm the diagnostic power of FSBP for the vascular component of HAVS reported by a few other investigators.

Provocative work experiences predict the acquired capability for suicide in physicians.

PubMed

Fink-Miller, Erin L

2015-09-30

The interpersonal psychological theory of suicidal behavior (IPTS) offers a potential means to explain suicide in physicians. The IPTS posits three necessary and sufficient precursors to death by suicide: thwarted belongingness, perceived burdensomeness, and acquired capability. The present study sought to examine whether provocative work experiences unique to physicians (e.g., placing sutures, withdrawing life support) would predict levels of acquired capability, while controlling for gender and painful and provocative experiences outside the work environment. Data were obtained from 376 of 7723 recruited physicians. Study measures included the Acquired Capability for Suicide Scale, the Interpersonal Needs Questionnaire, the Painful and Provocative Events Scale, and the Life Events Scale-Medical Doctors Version. Painful and provocative events outside of work predicted acquired capability (β=0.23, t=3.82, p<0.001, f(2)=0.09) as did provocative work experiences (β=0.12, t=2.05, p<0.05, f(2)=0.07). This represents the first study assessing the potential impact of unique work experiences on suicidality in physicians. Limitations include over-representation of Caucasian participants, limited representation from various specialties of medicine, and lack of information regarding individual differences. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Adenosine A1 Receptors in Mouse Pontine Reticular Formation Depress Breathing, Increase Anesthesia Recovery Time, and Decrease Acetylcholine Release

PubMed Central

Gettys, George C.; Liu, Fang; Kimlin, Ed; Baghdoyan, Helen A.; Lydic, Ralph

2012-01-01

Background Clinical and preclinical data demonstrate the analgesic actions of adenosine. Central administration of adenosine agonists, however, suppresses arousal and breathing by poorly understood mechanisms. This study tested the two-tailed hypothesis that adenosine A1 receptors in the pontine reticular formation (PRF) of C57BL/6J mice modulate breathing, behavioral arousal, and PRF acetylcholine release. Methods Three sets of experiments used 51 mice. First, breathing was measured by plethysmography after PRF microinjection of the adenosine A1 receptor agonist N6-sulfophenyl adenosine (SPA) or saline. Second, mice were anesthetized with isoflurane and time to recovery of righting response (RoRR) was quantified after PRF microinjection of SPA or saline. Third, acetylcholine release in the PRF was measured before and during microdialysis delivery of SPA, the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), or SPA and DPCPX. Results First, SPA significantly decreased respiratory rate (−18%), tidal volume (−12%) and minute ventilation (−16%). Second, SPA concentration accounted for 76% of the variance in RoRR. Third, SPA concentration accounted for a significant amount of the variance in acetylcholine release (52%), RoRR (98%), and breathing rate (86%). DPCPX alone caused a concentration-dependent increase in acetylcholine, decrease in RoRR, and decrease in breathing rate. Coadministration of SPA and DPCPX blocked the SPA-induced decrease in acetylcholine and increase in RoRR. Conclusions Endogenous adenosine acting at adenosine A1 receptors in the PRF modulates breathing, behavioral arousal, and acetylcholine release. The results support the interpretation that an adenosinergic-cholinergic interaction within the PRF comprises one neurochemical mechanism underlying the wakefulness stimulus for breathing. PMID:23263018

IRAP inhibition using HFI419 prevents moderate to severe acetylcholine mediated vasoconstriction in a rabbit model.

PubMed

El-Hawli, Aisha; Qaradakhi, Tawar; Hayes, Alan; Rybalka, Emma; Smith, Renee; Caprnda, Martin; Opatrilova, Radka; Gazdikova, Katarina; Benckova, Maria; Kruzliak, Peter; Zulli, Anthony

2017-02-01

Coronary artery vasospasm (constriction) caused by reduced nitric oxide bioavailability leads to myocardial infarction. Reduced endothelial release of nitric oxide by the neurotransmitter acetylcholine, leads to paradoxical vasoconstriction as it binds to smooth muscle cell M3 receptors. Thus, inhibition of coronary artery vasospasm will improve clinical outcomes. Inhibition of insulin regulated aminopeptidase has been shown to improve vessel function, thus we tested the hypothesis that HFI419, an inhibitor of insulin regulated aminopeptidase, could reduce blood vessel constriction to acetylcholine. The abdominal aorta was excised from New Zealand white rabbits (n=15) and incubated with 3mM Hcy to induce vascular dysfunction in vitro for 1h. HFI419 was added 5min prior to assessment of vascular function by cumulative doses of acetylcholine. In some rings, vasoconstriction to acetylcholine was observed in aortic rings after pre-incubation with 3mM homocysteine. Incubation with HFI419 inhibited the vasoconstrictive response to acetylcholine, thus improving, but not normalizing, vascular function (11.5±8.9% relaxation vs 79.2±37% constriction, p<0.05). Similarly, in another group with mild vasoconstriction, HFI419 inhibited this effect (34.9±4.6% relaxation vs 11.1±5.2%, constriction, p<0.05). HFI419 had no effect on control aorta or aorta with mild aortic dysfunction. The present study shows that HFI419 prevents acetylcholine mediated vasoconstriction in dysfunctional blood vessels. HFI419 had no effect on normal vasodilation. Our results indicate a therapeutic potential of HFI419 in reducing coronary artery vasospasm. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A potentially novel nicotinic receptor in Aplysia neuroendocrine cells.

PubMed

White, Sean H; Carter, Christopher J; Magoski, Neil S

2014-07-15

Nicotinic receptors form a diverse group of ligand-gated ionotropic receptors with roles in both synaptic transmission and the control of excitability. In the bag cell neurons of Aplysia, acetylcholine activates an ionotropic receptor, which passes inward current to produce a long-lasting afterdischarge and hormone release, leading to reproduction. While testing the agonist profile of the cholinergic response, we observed a second current that appeared to be gated only by nicotine and not acetylcholine. The peak nicotine-evoked current was markedly smaller in magnitude than the acetylcholine-induced current, cooperative (Hill value of 2.7), had an EC50 near 500 μM, readily recovered from desensitization, showed Ca(2+) permeability, and was blocked by mecamylamine, dihydro-β-erythroidine, or strychnine, but not by α-conotoxin ImI, methyllycaconitine, or hexamethonium. Aplysia transcriptome analysis followed by PCR yielded 20 full-length potential nicotinic receptor subunits. Sixteen of these were predicted to be cation selective, and real-time PCR suggested that 15 of the 16 subunits were expressed to varying degrees in the bag cell neurons. The acetylcholine-induced current, but not the nicotine current, was reduced by double-strand RNA treatment targeted to both subunits ApAChR-C and -E. Conversely, the nicotine-evoked current, but not the acetylcholine current, was lessened by targeting both subunits ApAChR-H and -P. To the best of our knowledge, this is the first report suggesting that a nicotinic receptor is not gated by acetylcholine. Separate receptors may serve as a means to differentially trigger plasticity or safeguard propagation by assuring that only acetylcholine, the endogenous agonist, initiates large enough responses to trigger reproduction. Copyright © 2014 the American Physiological Society.

Adenosine A(1) receptors in mouse pontine reticular formation depress breathing, increase anesthesia recovery time, and decrease acetylcholine release.

PubMed

Gettys, George C; Liu, Fang; Kimlin, Ed; Baghdoyan, Helen A; Lydic, Ralph

2013-02-01

Clinical and preclinical data demonstrate the analgesic actions of adenosine. Central administration of adenosine agonists, however, suppresses arousal and breathing by poorly understood mechanisms. This study tested the two-tailed hypothesis that adenosine A1 receptors in the pontine reticular formation (PRF) of C57BL/6J mice modulate breathing, behavioral arousal, and PRF acetylcholine release. Three sets of experiments used 51 mice. First, breathing was measured by plethysmography after PRF microinjection of the adenosine A1 receptor agonist N-sulfophenyl adenosine (SPA) or saline. Second, mice were anesthetized with isoflurane and the time to recovery of righting response (RoRR) was quantified after a PRF microinjection of SPA or saline. Third, acetylcholine release in the PRF was measured before and during microdialysis delivery of SPA, the adenosine A1 receptor antagonist 1, 3-dipropyl-8-cyclopentylxanthine, or SPA and 1, 3-dipropyl-8-cyclopentylxanthine. First, SPA significantly decreased respiratory rate (-18%), tidal volume (-12%), and minute ventilation (-16%). Second, SPA concentration accounted for 76% of the variance in RoRR. Third, SPA concentration accounted for a significant amount of the variance in acetylcholine release (52%), RoRR (98%), and breathing rate (86%). 1, 3-dipropyl-8-cyclopentylxanthine alone caused a concentration-dependent increase in acetylcholine, a decrease in RoRR, and a decrease in breathing rate. Coadministration of SPA and 1, 3-dipropyl-8-cyclopentylxanthine blocked the SPA-induced decrease in acetylcholine and increase in RoRR. Endogenous adenosine acting at adenosine A1 receptors in the PRF modulates breathing, behavioral arousal, and acetylcholine release. The results support the interpretation that an adenosinergic-cholinergic interaction within the PRF comprises one neurochemical mechanism underlying the wakefulness stimulus for breathing.

[Gold salt alveolitis in 3 patients with rheumatoid arthritis].

PubMed

Music, E; Tomsic, M; Logar, D

1995-06-01

When the characteristic symptoms for an interstitial pulmonary disease arise in patients with rheumatoid arthritis, a drug-induced alveolitis should be considered in the differential diagnosis. In such cases, the administration of the drug and gold salts should be stopped. The cases of three patients with rheumatoid arthritis (RA) who had been treated with gold salts for 2 months (A), 23 months (B), and 36 months (C) are presented. The total dose of sodium aureothiomalate amounted to 280 mg for patient A, 1150 mg for patient B, and 2190 mg for patient C. Clinical signs, X-rays of the lungs, pulmonary function tests, and laboratory tests were evaluated for the three patients while, for patient A BAL as well as provocation tests were additionally performed before and after therapy. In this case, the histological picture of the lungs is presented; biopsies were taken during the first BAL. The clinical complaints of all 3 patients were similar, with the alveolitis being observed as diffuse in one case and above all in the upper regions in two cases on radiology. This led to differing degrees of diffusion disorders in the lungs. In patient A, the diagnosis was made in the stage of progressive fibrotic alveolitis and was treated with D-penicillamine. All 3 patients received steroids over 3-6 months and the gold salts were stopped. Because of the long duration and doubtful differential diagnosis for patient A with either rheumatoid lung or gold salt alveolitis, a provocation test with sodium aureothiomalate was performed. All 3 patients had blood eosinophilia while, in case A, a thrombopenia was also found. A gold salt alveolitis can occur as a side effect of gold salts in addition to skin vasculitis and hematological disorders. When the gold salt administration is not stopped a fibrotic alveolitis can develop. The provocation test can be diagnostically useful to distinguish between a rheumatoid lung and gold salt alveolitis.

Diagnostic testing of dogs for food hypersensitivity.

PubMed

Jeffers, J G; Shanley, K J; Meyer, E K

1991-01-15

Thirteen food-allergic dogs were studied to evaluate the efficacy of feeding a commercially available egg and rice diet, intradermal skin testing, and serologic testing by ELISA for diagnosing and/or characterizing food hypersensitivity. Feeding of a home-cooked whole lamb meat and rice diet for 3 weeks, followed by challenge with each dog's regular diet, served as the standard for diagnosing food hypersensitivity. Each dog underwent provocative testing with 6 individual ingredients to determine as many of its dietary allergens as possible. Prior to skin testing and serologic testing by ELISA, most dogs had been recently exposed to the offending diet and subsequently manifested clinical signs of allergy. All dogs that tolerated the aforementioned commercial diet were exposed to it for at least 7 weeks; 84.6% of food-hypersensitive dogs ate the commercial diet with impunity. Of the 2 reactors to the commercial diet, only 1 became pruritic in response to provocation testing with chicken eggs. Low sensitivity and high specificity were found for skin testing and the ELISA, indicating a lack of true- and false-positive reactions. Neither the positive nor negative predictive values adequately predicted positive and negative reactions, respectively, for either test. On the basis of these results, the commercial diet, skin testing, and anti-IgE ELISA cannot replace an owner-prepared food elimination diet for food hypersensitivity testing in dogs.

Radiochemical micro assays for the determination of choline acetyltransferase and acetylcholinesterase activities

PubMed Central

Fonnum, F.

1969-01-01

1. The methods for the assay of choline acetyltransferase were based on the reaction between labelled acetyl-CoA and unlabelled choline to give labelled acetylcholine. 2. Both synthetic acetyl-CoA and acetyl-CoA formed from sodium [1-14C]acetate or sodium [3H]acetate by incubation with CoA, ATP, Mg2+ and extract from acetone-dried pigeon liver were used. 3. [1-14C]Acetylcholine was isolated by extraction with ketonic sodium tetraphenylboron. 4. [3H]Acetylcholine was precipitated with sodium tetraphenylboron to remove a ketone-soluble contaminant in sodium [3H]acetate and then extracted with ketonic sodium tetraphenylboron. 5. The values of choline acetyltransferase activity obtained in the presence of sodium cyanide or EDTA and synthetic acetyl-CoA were similar to those obtained with acetyl-CoA synthesized in situ. 6. The assay of acetylcholinesterase was based on the formation of labelled acetate from labelled acetylcholine. The labelled acetylcholine could be quantitatively removed from the acetate by extraction with ketonic sodium tetraphenylboron. 7. The methods were tested with samples from central and peripheral nervous tissues and purified enzymes. 8. The blank values for choline acetyltransferase and acetylcholinesterase corresponded to the activities in 20ng. and 5ng. of brain tissue respectively. PMID:4982085

Pravastatin and endothelium dependent vasomotion after coronary angioplasty: the PREFACE trial

PubMed Central

Mulder, H; Schalij, M; Kauer, B; Visser, R; van Dijkman, P R M; Jukema, J; Zwinderman, A; Bruschke, A

2001-01-01

OBJECTIVE—To test the hypothesis that the 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor pravastatin ameliorates endothelium mediated responses of dilated coronary segments: the PREFACE (pravastatin related effects following angioplasty on coronary endothelium) trial.
DESIGN—A double blind, randomised, placebo controlled, multicentre study.
SETTING—Four hospitals in the Netherlands.
PATIENTS—63 non-smoking, non-hypercholesterolaemic patients scheduled for elective balloon angioplasty (pravastatin 34, placebo 29).
INTERVENTIONS—The effects of three months of pravastatin treatment (40 mg daily) on endothelium dependent vasomotor function were studied. Balloon angioplasty was undertaken one month after randomisation, and coronary vasomotor function tests using acetylcholine were performed two months after balloon angioplasty. The angiograms were analysed quantitatively.
MAIN OUTCOME MEASURES—The efficacy measure was the acetylcholine induced change in mean arterial diameter, determined in the dilated segment and in an angiographically normal segment of an adjacent non-manipulated coronary artery.
RESULTS—Increasing acetylcholine doses produced vasoconstriction in the dilated segments (p = 0.004) but not in the normal segments. Pravastatin did not affect the vascular response to acetylcholine in either the dilated segments (p = 0.09) or the non-dilated sites. Endothelium dependent vasomotion in normal segments was correlated with that in dilated segments (r = 0.47, p < 0.001). There were fewer procedure related events in the pravastatin group than in the placebo group (p < 0.05).
CONCLUSIONS—Endothelium dependent vasomotion in normal segments is correlated with that in dilated segments. A significant beneficial effect of pravastatin on endothelial function could not be shown, but in the dilated segments there was a trend towards a beneficial treatment effect in the pravastatin group.


Keywords: angioplasty; endothelium; acetylcholine; pravastatin PMID:11602546

Exogenous cortisol facilitates responses to social threat under high provocation.

PubMed

Bertsch, Katja; Böhnke, Robina; Kruk, Menno R; Richter, Steffen; Naumann, Ewald

2011-04-01

Stress is one of the most important promoters of aggression. Human and animal studies have found associations between basal and acute levels of the stress hormone cortisol and (abnormal) aggression. Irrespective of the direction of these changes--i.e., increased or decreased aggressive behavior--the results of these studies suggest dramatic alterations in the processing of threat-related social information. Therefore, the effects of cortisol and provocation on social information processing were addressed by the present study. After a placebo-controlled pharmacological manipulation of acute cortisol levels, we exposed healthy individuals to high or low levels of provocation in a competitive aggression paradigm. Influences of cortisol and provocation on emotional face processing were then investigated with reaction times and event-related potentials (ERPs) in an emotional Stroop task. In line with previous results, enhanced early and later positive, posterior ERP components indicated a provocation-induced enhanced relevance for all kinds of social information. Cortisol, however, reduced an early frontocentral bias for angry faces and--despite the provocation-enhancing relevance--led to faster reactions for all facial expressions in highly provoked participants. The results thus support the moderating role of social information processing in the 'vicious circle of stress and aggression'. Copyright © 2010 Elsevier Inc. All rights reserved.

Effects of individual strengthening exercises for the stabilization muscles on the nutation torque of the sacroiliac joint in a sedentary worker with nonspecific sacroiliac joint pain.

PubMed

Yoo, Won-Gyu

2015-01-01

[Purpose] We investigated the effects of individual strengthening exercises for the stabilization muscles on the nutation torque of the sacroiliac joint in a sedentary worker with nonspecific sacroiliac joint pain. [Subject] A 36-year-old female complained of pain in the sacroiliac joints. [Methods] The subject performed individual strengthening exercises for the stabilization muscles for nutation torque of the sacroiliac joint for 3 weeks. Pain-provocation tests and visual analog scale (VAS) scores were evaluated before and after the exercises. [Results] After performing the individual strengthening exercises for the erector spinae, rectus abdominis, and biceps femoris muscles for 3 weeks, the subject displayed no pain in the pain provocation tests, and the VAS score was 2/10. [Conclusion] The individual strengthening exercises for the stabilization muscles of the sacroiliac joint performed in the present study appear to be effective for sedentary workers with sacroiliac joint pain.

β-Amyloid-acetylcholine molecular interaction: new role of cholinergic mediators in anti-Alzheimer therapy?

PubMed

Grimaldi, Manuela; Marino, Sara Di; Florenzano, Fulvio; Ciotta, Maria Teresa; Nori, Stefania Lucia; Rodriquez, Manuela; Sorrentino, Giuseppe; D'Ursi, Anna Maria; Scrima, Mario

2016-07-01

For long time Alzheimer's disease has been attributed to a cholinergic deficit. More recently, it has been considered dependent on the accumulation of the amyloid beta peptide (Aβ), which promotes neuronal loss and impairs neuronal function. Results/methodology: In the present study, using biophysical and biochemical experiments we tested the hypothesis that in addition to its role as a neurotransmitter, acetylcholine may exert its action as an anti-Alzheimer agent through a direct interaction with Aβ. Our data provide evidence that acetylcholine favors the soluble peptide conformation and exerts a neuroprotective effect against the neuroinflammatory and toxic effects of Aβ. The present paper paves the way toward the development of new polyfunctional anti-Alzheimer therapeutics capable of intervening on both the cholinergic transmission and the Aβ aggregation.

Concomitant Release of Ventral Tegmental Acetylcholine and Accumbal Dopamine by Ghrelin in Rats

PubMed Central

Jerlhag, Elisabet; Janson, Anna Carin; Waters, Susanna; Engel, Jörgen A.

2012-01-01

Ghrelin, an orexigenic peptide, regulates energy balance specifically via hypothalamic circuits. Growing evidence suggest that ghrelin increases the incentive value of motivated behaviours via activation of the cholinergic-dopaminergic reward link. It encompasses the cholinergic afferent projection from the laterodorsal tegmental area (LDTg) to the dopaminergic cells of the ventral tegmental area (VTA) and the mesolimbic dopamine system projecting from the VTA to nucleus accumbens (N.Acc.). Ghrelin receptors (GHS-R1A) are expressed in these reward nodes and ghrelin administration into the LDTg increases accumbal dopamine, an effect involving nicotinic acetylcholine receptors in the VTA. The present series of experiments were undertaken directly to test this hypothesis. Here we show that ghrelin, administered peripherally or locally into the LDTg concomitantly increases ventral tegmental acetylcholine as well as accumbal dopamine release. A GHS-R1A antagonist blocks this synchronous neurotransmitter release induced by peripheral ghrelin. In addition, local perfusion of the unselective nicotinic antagonist mecamylamine into the VTA blocks the ability of ghrelin (administered into the LDTg) to increase N.Acc.-dopamine, but not VTA-acetylcholine. Collectively our data indicate that ghrelin activates the LDTg causing a release of acetylcholine in the VTA, which in turn activates local nicotinic acetylcholine receptors causing a release of accumbal dopamine. Given that a dysfunction in the cholinergic-dopaminergic reward system is involved in addictive behaviours, including compulsive overeating and alcohol use disorder, and that hyperghrelinemia is associated with such addictive behaviours, ghrelin-responsive circuits may serve as a novel pharmacological target for treatment of alcohol use disorder as well as binge eating. PMID:23166710

Administration of arginine plus growth hormone releasing hormone to evaluate growth hormone (GH) secretory status in children with GH deficiency.

PubMed

Keller, A; Donaubauer, J; Kratzsch, J; Pfaeffle, R; Hirsch, W; Kiess, W; Keller, E

2007-12-01

Diagnosis of growth hormone deficiency (GHD) in childhood is usually based on growth hormone (GH) response to at least two provocative stimuli. The aim of this study was to determine whether sequential administration of arginine (Arg) plus GH releasing hormone (GHRH) could be a useful tool in evaluating GHD in children. Thirty patients with short stature (mean age 9.0 years) with decreased growth rate were tested for GHD with Arg and the insulin tolerance test (ITT). Patients with confirmed GHD (peak GH <8 ng/ml) were subsequently tested with Arg + GHRH. Maximum GH stimulation for Arg and ITT was 6.3 (1.0-7.8) and 6.7 (0.5-7.7) ng/ml, respectively. Peak GH for the Arg + GHRH test was 36.3 (4.3-84.5) ng/ml and significantly different from the other provocative tests. Peak GH values for the three tests were not significantly correlated between tests or with clinical parameters. There were no significant differences in Arg + GHRH results between children with or without abnormal hypothalamic-pituitary MRI scans. Arg + GHRH gave higher GH levels than insulin or Arg alone. Because of the different causes of childhood GHD (hypothalamic and/or pituitary dysfunction), the Arg + GHRH test is unsuitable .for evaluating GHD and deciding whether GH replacement therapy is indicated.

Control of synthesis and release of radioactive acetylcholine in brain slices from the rat. Effects of neurotropic drugs

PubMed Central

Grewaal, D. S.; Quastel, J. H.

1973-01-01

1. Studies of the synthesis and release of radioactive acetylcholine in rat brain-cortex slices incubated in Locke–bicarbonate–[U-14C]glucose media, containing paraoxon as cholinesterase inhibitor, revealed the following phenomena: (a) dependence of K+-or protoveratrine-stimulated acetylcholine synthesis and release on the presence of Na+ and Ca2+ in the incubation medium, (b) enhanced release of radioactive acetylcholine by substances that promote depolarization at the nerve cell membrane (e.g. high K+, ouabain, protoveratrine, sodium l-glutamate, high concentration of acetylcholine), (c) failure of acetylcholine synthesis to keep pace with acetylcholine release under certain conditions (e.g. the presence of ouabain or lack of Na+). 2. Stimulation by K+ of radioactive acetylcholine synthesis was directly proportional to the external concentration of Na+, but some synthesis and release of radioactive acetylcholine occurred in the absence of Na+ as well as in the absence of Ca2+. 3. The Na+ dependence of K+-stimulated acetylcholine synthesis was partly due to suppression of choline transport, as addition of small concentrations of choline partly neutralized the effect of Na+ lack, and partly due to the suppression of the activity of the Na+ pump. 4. Protoveratrine caused a greatly increased release of radioactive acetylcholine without stimulating total radioactive acetylcholine synthesis. Protoveratrine was ineffective in the absence of Ca2+ from the incubation medium. It completely blocked K+ stimulation of acetylcholine synthesis and release. 5. Tetrodotoxin abolished the effects of protoveratrine on acetylcholine release. It had blocking effects (partial or complete) on the action of high K+, sodium l-glutamate and lack of Ca2+ on acetylcholine synthesis and release. 6. Unlabelled exogenous acetylcholine did not diminish the content of labelled tissue acetylcholine, derived from labelled glucose, suggesting that no exchange with vesicular acetylcholine took place. In the presence of 4mm-KCl it caused some increase in the release of labelled acetylcholine. 7. The barbiturates (Amytal, pentothal), whilst having no significant effects on labelled acetylcholine synthesis in unstimulated brain except at high concentration (1mm), diminished or abolished (at 0.25 or 0.5mm) the enhanced release of acetylcholine, due to high K+ or lack of Ca2+. The fall in tissue content of acetylcholine, due to lack of Ca2+, was diminished or abolished by pentothal (0.25 or 0.5mm) or Amytal (0.25mm). PMID:4722896

Provocation of left ventricular outflow tract obstruction using nitrate inhalation in hypertrophic cardiomyopathy: Relation to electromechanical delay.

PubMed

Badran, Hala Mahfouz; Ibrahim, Waleed Abdou; Faheem, Naglaa; Yassin, Rehab; Alashkar, Tamer; Yacoub, Magdi

2015-01-01

Left ventricular outflow tract obstruction (LVOT) is an independent predictor of adverse outcome in hypertrophic cardiomyopathy (HCM). It is of major importance that the provocation modalities used are validated against each other. To define the magnitude of LVOT gradients provocation during both isosorbide dinitrate (ISDN) inhalation and treadmill exercise in non-obstructive HCM and analyze the correlation to the electromechanical delay using speckle tracking. We studied 39 HCM pts (64% males, mean age 38 ± 13 years) regional LV longitudinal strain and electromechanical delay (TTP) was analyzed at rest using speckle tracking. LVOT gradient was measured at rest and after ISDN then patients underwent a treadmill exercise echocardiography (EE) and LVOT gradient was measured at peak exercise. The maximum effect of ISDN on LVOT gradient was obtained at 5 minutes, it increased to a significant level in 12 (31%) patients, and in 14 (36%) patients using EE, with 85.6% sensitivity & 100% specificity. Patients with latent obstruction had larger left atrial volume and lower E/A ratio compared to the non-obstructive group (p < 0.01). LVOTG using ISDN was significantly correlated with that using EE (p < 0.0001), resting LVOTG (p < 0.0001), SAM (p < 0.0001), EF% (p < 0.02) and regional electromechanical delay but not related to global LV longitudinal strain. Using multivariate regression, resting LVOTG (p = 0.006) & TTP mid septum (p = 0.01) were found to be independent predictors of latent LVOT obstruction using ISDN. There is a comparable diagnostic value of nitrate inhalation to exercise testing in provocation of LVOT obstruction in HCM. Latent obstruction is predominantly dependent on regional electromechanical delay.

Provocation of left ventricular outflow tract obstruction using nitrate inhalation in hypertrophic cardiomyopathy: Relation to electromechanical delay

PubMed Central

Badran, Hala Mahfouz; Ibrahim, Waleed Abdou; Faheem, Naglaa; Yassin, Rehab; Alashkar, Tamer; Yacoub, Magdi

2015-01-01

Background: Left ventricular outflow tract obstruction (LVOT) is an independent predictor of adverse outcome in hypertrophic cardiomyopathy (HCM). It is of major importance that the provocation modalities used are validated against each other. Aim: To define the magnitude of LVOT gradients provocation during both isosorbide dinitrate (ISDN) inhalation and treadmill exercise in non-obstructive HCM and analyze the correlation to the electromechanical delay using speckle tracking. Methods: We studied 39 HCM pts (64% males, mean age 38 ± 13 years) regional LV longitudinal strain and electromechanical delay (TTP) was analyzed at rest using speckle tracking. LVOT gradient was measured at rest and after ISDN then patients underwent a treadmill exercise echocardiography (EE) and LVOT gradient was measured at peak exercise. Results: The maximum effect of ISDN on LVOT gradient was obtained at 5 minutes, it increased to a significant level in 12 (31%) patients, and in 14 (36%) patients using EE, with 85.6% sensitivity & 100% specificity. Patients with latent obstruction had larger left atrial volume and lower E/A ratio compared to the non-obstructive group (p < 0.01). LVOTG using ISDN was significantly correlated with that using EE (p < 0.0001), resting LVOTG (p < 0.0001), SAM (p < 0.0001), EF% (p < 0.02) and regional electromechanical delay but not related to global LV longitudinal strain. Using multivariate regression, resting LVOTG (p = 0.006) & TTP mid septum (p = 0.01) were found to be independent predictors of latent LVOT obstruction using ISDN. Conclusion: There is a comparable diagnostic value of nitrate inhalation to exercise testing in provocation of LVOT obstruction in HCM. Latent obstruction is predominantly dependent on regional electromechanical delay. PMID:26779503

Psychophysical and vasomotor evidence for interdependency of TRPA1 and TRPV1 nociceptive responses in human skin: an experimental study.

PubMed

Nielsen, Thomas Arendt; Eriksen, Matilde Alida; Gazerani, Parisa; Andersen, Hjalte Holm

2018-05-25

The TRPA1 and TRPV1 receptors are important pharmaceutical targets for antipruritic and analgesic therapy. Obtaining further knowledge on their roles and inter-relationship in humans is therefore crucial. Preclinical results are contradictory concerning co-expression and functional interdependency of TRPV1 and TRPA1 but no human evidence exists. This human experimental study investigated whether functional responses from the subpopulation of TRPA1-nociceptors could be evoked following defunctionalization of TRPV1-nociceptors by cutaneous application of high-concentration capsaicin. Two quadratic areas on each forearm were randomized to pretreatment with an 8% topical capsaicin patch or vehicle for 24h. Subsequently, areas were provoked by transdermal 1% topical capsaicin (TRPV1 agonist) or 10% topical allyl-isothiocyanate ('AITC', a TRPA1-agonist), delivered by 12mm Finn chambers. Evoked pain intensities were recorded during pretreatments and chemical provocations. Quantitative sensory tests were performed before and after provocations to assess changes of heat pain sensitivity. Imaging of vasomotor responses was used to assess neurogenic inflammation after the chemical provocations. In the capsaicin-pretreated areas both the subsequent 1% capsaicin- and 10% AITC-provoked pain intensities were inhibited by 92.9±2.5% and 86.9±5.0% (both: P<0.001), respectively. The capsaicin-ablated skin areas showed significant heat hypoalgesia at baseline (P<0.001) as well as heat antihyperalgesia, and inhibition of neurogenic inflammation evoked by both 1% capsaicin- and 10% AITC provocations (both: P<0.001). Ablation of capsaicin-sensitive afferents caused consistent and equal inhibition of both TRPV1 and TRPA1-provoked responses assessed psychophysically and by imaging of vasomotor responses. The present study suggests that TRPA1 nociceptive responses in human skin strongly depend on intact capsaicin-sensitive, TPRV1 fibers.

Validity and Measurement

ERIC Educational Resources Information Center

Maraun, Michael D.

2012-01-01

As illuminated forcefully by Professor Newton's provocative analytical and historical excursion, as long as tests are employed to practical ends (prediction, selection, etc.) there is little cause for the metatheoretic angst that occasions rounds of papers on the topic of validity. But then, also, there seems little need, within this context of…

[Growth rate and bone maturation in celiac disease (author's transl)].

PubMed

Martínez Sopena, M J; Calvo Romero, M C; Bedate Calderón, P; Alonso Franch, M; Sánchez Villares, E

1978-05-01

The growth and bone maturation of 43 celiac patients were analyzed. A significant correlation between gluten intake and growth rate was found. The authors suggest this is a good parameter to advise the best moment to make the control biopsie and the provocation test.

EVP-6124, a novel and selective α7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of α7 nicotinic acetylcholine receptors.

PubMed

Prickaerts, Jos; van Goethem, Nick P; Chesworth, Richard; Shapiro, Gideon; Boess, Frank G; Methfessel, Christoph; Reneerkens, Olga A H; Flood, Dorothy G; Hilt, Dana; Gawryl, Maria; Bertrand, Sonia; Bertrand, Daniel; König, Gerhard

2012-02-01

EVP-6124, (R)-7-chloro-N-quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide, is a novel partial agonist of α7 neuronal nicotinic acetylcholine receptors (nAChRs) that was evaluated here in vitro and in vivo. In binding and functional experiments, EVP-6124 showed selectivity for α7 nAChRs and did not activate or inhibit heteromeric α4β2 nAChRs. EVP-6124 had good brain penetration and an adequate exposure time. EVP-6124 (0.3 mg/kg, p.o.) significantly restored memory function in scopolamine-treated rats (0.1 mg/kg, i.p.) in an object recognition task (ORT). Although donepezil at 0.1 mg/kg, p.o. or EVP-6124 at 0.03 mg/kg, p.o. did not improve memory in this task, co-administration of these sub-efficacious doses fully restored memory. In a natural forgetting test, an ORT with a 24 h retention time, EVP-6124 improved memory at 0.3 mg/kg, p.o. This improvement was blocked by the selective α7 nAChR antagonist methyllycaconitine (0.3 mg/kg, i.p. or 10 μg, i.c.v.). In co-application experiments of EVP-6124 with acetylcholine, sustained exposure to EVP-6124 in functional investigations in oocytes caused desensitization at concentrations greater than 3 nM, while lower concentrations (0.3-1 nM) caused an increase in the acetylcholine-evoked response. These actions were interpreted as representing a co-agonist activity of EVP-6124 with acetylcholine on α7 nAChRs. The concentrations of EVP-6124 that resulted in physiological potentiation were consistent with the free drug concentrations in brain that improved memory performance in the ORT. These data suggest that the selective partial agonist EVP-6124 improves memory performance by potentiating the acetylcholine response of α7 nAChRs and support new therapeutic strategies for the treatment of cognitive impairment. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.

Aggression in Children with Conduct Problems and Callous-Unemotional Traits: Social Information Processing and Response to Peer Provocation.

PubMed

Helseth, Sarah A; Waschbusch, Daniel A; King, Sara; Willoughby, Michael T

2015-11-01

Callous/unemotional traits (CU) moderate children's conduct problems (CP) in numerous domains, including social functioning. The present study examined whether CU traits also moderate the aggressiveness of children's social information processing (SIP) and responses to varying intensities of peer provocation. Sixty elementary school-age children (46 males) were grouped into those without CP or CU (controls, n = 32), those with CP but not CU (CP-only; n = 14), and those with both CP and CU (CPCU, n = 14). Participants completed a task that measured two aspects of SIP (response generation and hostile attribution bias) and a computerized reaction time task (CRTT) that measured behavior, affect, and communication before and after provocation under instrumental and hostile aggressive conditions. Children with CPCU generated more aggressive responses than controls on measures of SIP. On the CRTT, all children exhibited reactive aggression following high provocation, but only children with CPCU exhibited proactive aggression, and reactive aggression following low provocation; no differences in affect were found. In a series of exploratory analyses, CPCU children communicated antisocially, while CP-only communicated prosocially. Finally, children with CPCU did not seem to hold a grudge following the final instance of provocation, instead gradually returning to baseline like their non-CU peers. These distinct social cognitive and behavioral profiles hint at different etiologies of CP and CPCU, underscoring the variability of aggression in these populations.

Standing Vs Supine; Does it Matter in Cough Stress Testing?

PubMed

Patnam, Radhika; Edenfield, Autumn L; Swift, Steven E

The aim of this study was to compare the sensitivity of cough stress test in the standing versus supine position in the evaluation of incontinent females. We performed a prospective observational study of women with the chief complaint of urinary incontinence (UI) undergoing a provocative cough stress test (CST). Subjects underwent both a standing and a supine CST. Testing order was randomized via block randomization. Cough stress test was performed in a standard method via backfill of 200 mL or until the subject described strong urge. The subjects were asked to cough, and the physician documented urine leakage by direct observation. The gold standard for stress UI diagnosis was a positive CST in either position. Sixty subjects were enrolled, 38 (63%) tested positive on any CST, with 38 (63%) positive on standing compared with 29 (28%) positive on supine testing. Nine women (15%) had positive standing and negative supine testing. No subjects had negative standing with positive supine testing. There were no significant differences in positive tests between the 2 randomized groups (standing first and supine second vs. supine first and standing second). When compared with the gold standard of any positive provocative stress test, the supine CST has a sensitivity of 76%, whereas the standing CST has a sensitivity of 100%. The standing CST is more sensitive than the supine CST and should be performed in any patient with a complaint of UI and negative supine CST. The order of testing either supine or standing first does not affect the results.

Physical aggression as a function of perceived fighting ability and provocation: an experimental investigation.

PubMed

Archer, John; Benson, David

2008-01-01

In three studies, Resource Holding Power (RHP) and provocation were manipulated in scenarios involving a young person in a bar with friends. In Study 1, teenage men reported lower likelihood of responding with physical aggression when insulted as levels of three RHP cues (size, allies and reputation) increased, effects that were accentuated by combinations of high-RHP cues; in the second part of this study, they consistently rated an insult to their girlfriend as the most provoking from a range of possible provocations, chosen on theoretical and empirical grounds. Study 2 replicated the results of the first part of Study 1 in samples of men and women in their twenties, although the effects were weaker at low levels of RHP. Study 3 combined a high- or low-provoking event, with low, medium or high RHP, and a wider range of response choices. As expected, direct aggression increased as provocation increased and RHP decreased. Delayed aggressive responses, including revenge fantasies, were highest in response to high provocation and high RHP. Findings are discussed in relation to theoretical models of aggressive motivation. (c) 2007 Wiley-Liss, Inc.

[Adrenomedullin--the link between the sympathetic nervous system activation and peripheral vasodilatation in some patients with vasovagal syncope].

PubMed

Gajek, Jacek; Zyśko, Dorota; Halawa, Bogumił

2004-09-01

Adrenomedullin (ADM) is a potent vasodilator playing role in regulation of central hemodynamic. The concentration of plasma ADM in healthy people increases under the influence of orthostatic stress. In patients with vasovagal syncope (VS) the changes in ADM concentration could be responsible either for syncope provocation or prevention. The aim of the study was to assess the influence of phase of the head-up tilt test (HUTT) in which the syncope occurred on the plasma concentration of ADM. The study was performed in 25 patients (pts) (18 women and 7 men), mean age 45.0+/-16.1 years with cardiodepressive reactions during HUTT according to the Italian protocol with nitroglycerine (NTG) provocation if necessary: Syncope was caused in 23 pts due to vasovagal reaction: in 17 pts syncope occurred after NTG provocation (group 1), and in 6 pts occurred in the passive phase of tilt (group 2a), in 2 pts due to dysautonomic reactions (group 2b). The head-up tilt test was performed according to ESC guidelines. The blood for ADM concentration was drawn after 30 min supine rest (ADM 1) and immediately after syncope (ADM 2). ADM level was measured using radioimmunological method. The results. In group 1 plasma level of ADM significantly decreased after the HUTT (3.2+/-3.4 vs 1.7+/-1,4 pg/0.1 ml; p<0.05) and in group 2a increased significantly (1.3+/-0.8 vs 2.7+/-1.3 pg/0.1 ml; p<0.05) comparing to baseline values. The ADM concentration did not differ between the groups in baseline conditions and was significantly higher after the syncope in group 2a (p<0.05). Conclusions. The excessive increase of ADM concentration during the passive phase of HUTT could play the causative role in pathogenesis of VS occurring early during the HUTT. In patients with VS after NTG provocation the decrease of ADM concentration can be the result of hemodynamic changes in the presence of vasodilating drug and may be the mechanism that could prevent the syncope.

Aqueous fraction of Beta vulgaris ameliorates hyperglycemia in diabetic mice due to enhanced glucose stimulated insulin secretion, mediated by acetylcholine and GLP-1, and elevated glucose uptake via increased membrane bound GLUT4 transporters.

PubMed

Ul Kabir, Ashraf; Samad, Mehdi Bin; Ahmed, Arif; Jahan, Mohammad Rajib; Akhter, Farjana; Tasnim, Jinat; Hasan, S M Nageeb; Sayfe, Sania Sarker; Hannan, J M A

2015-01-01

The study was designed to investigate the probable mechanisms of anti-hyperglycemic activity of B. Vulgaris. Aqueous fraction of B. Vulgaris extract was the only active fraction (50mg/kg). Plasma insulin level was found to be the highest at 30 mins after B. Vulgaris administration at a dose of 200mg/kg. B. Vulgaris treated mice were also assayed for plasma Acetylcholine, Glucagon Like Peptide-1 (GLP-1), Gastric Inhibitory Peptide (GIP), Vasoactive Intestinal Peptide, Pituitary Adenylate Cyclase-Activating Peptide (PACAP), Insulin Like Growth Factor-1 (IGF-1), Pancreatic Polypeptides (PP), and Somatostatin, along with the corresponding insulin levels. Plasma Acetylcholine and GLP-1 significantly increased in B. Vulgaris treated animals and were further studied. Pharmacological enhancers, inhibitors, and antagonists of Acetylcholine and GLP-1 were also administered to the test animals, and corresponding insulin levels were measured. These studies confirmed the role of acetylcholine and GLP-1 in enhanced insulin secretion (p<0.05). Principal signaling molecules were quantified in isolated mice islets for the respective pathways to elucidate their activities. Elevated concentrations of Acetylcholine and GLP-1 in B. Vulgaris treated mice were found to be sufficient to activate the respective pathways for insulin secretion (p<0.05). The amount of membrane bound GLUT1 and GLUT4 transporters were quantified and the subsequent glucose uptake and glycogen synthesis were assayed. We showed that levels of membrane bound GLUT4 transporters, glucose-6-phosphate in skeletal myocytes, activity of glycogen synthase, and level of glycogen deposited in the skeletal muscles all increased (p<0.05). Findings of the present study clearly prove the role of Acetylcholine and GLP-1 in the Insulin secreting activity of B. Vulgaris. Increased glucose uptake in the skeletal muscles and subsequent glycogen synthesis may also play a part in the anti-hyperglycemic activity of B. Vulgaris.

Esophageal motor function: technical aspects of manometry.

PubMed

Gyawali, C Prakash; Patel, Amit

2014-10-01

High-resolution manometry (HRM) has advanced the understanding of esophageal peristaltic mechanisms and has simplified esophageal motor testing. In this article the technical aspects of HRM are addressed, focusing on test protocols, in addition to concerns and pitfalls in performing esophageal motor studies. Specifically, catheter positioning, equipment-related artifacts, basal data acquisition, adequate swallows, and provocative maneuvers are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Metabolic myopathies

NASA Technical Reports Server (NTRS)

Martin, A.; Haller, R. G.; Barohn, R.; Blomqvist, C. G. (Principal Investigator)

1994-01-01

Metabolic myopathies are disorders of muscle energy production that result in skeletal muscle dysfunction. Cardiac and systemic metabolic dysfunction may coexist. Symptoms are often intermittent and provoked by exercise or changes in supply of lipid and carbohydrate fuels. Specific disorders of lipid and carbohydrate metabolism in muscle are reviewed. Evaluation often requires provocative exercise testing. These tests may include ischemic forearm exercise, aerobic cycle exercise, and 31P magnetic resonance spectroscopy with exercise.

Evaluation of canine adverse food reactions by patch testing with single proteins, single carbohydrates and commercial foods.

PubMed

Johansen, Cornelia; Mariani, Claire; Mueller, Ralf S

2017-10-01

Adverse food reaction (AFR) is an important differential diagnosis for the pruritic dog. It is usually diagnosed by feeding an elimination diet with a novel protein and carbohydrate source for eight weeks followed by subsequent food provocation. A previous study demonstrated that patch testing dogs with foods had a high sensitivity and negative predictability for selection of elimination diet ingredients. The aim of this study was to investigate patch testing with proteins, carbohydrates and dry commercial dog food in dogs to determine whether there was value in patch testing to aid the diagnosis of canine adverse food reaction. Twenty five privately owned dogs, with confirmed AFR, underwent provocation trials with selected food antigens and patch testing. For proteins, carbohydrates and dry dog food the sensitivity of patch testing was 100%, 70% and 22.2%, respectively; the negative predictive values of patch testing were 100%, 79% and 72%. The positive predictive values of patch testing for proteins and carbohydrates were 75% and 74%, respectively. This study confirmed that patch testing may be useful for the selection of a suitable protein source for an elimination diet in dogs with suspected AFR, but not as a diagnostic tool for canine AFR. Results for proteins are more reliable than for carbohydrates and the majority of positive patch test reactions were observed with raw protein. Patch testing with commercial dog food does not seem to be useful. © 2017 ESVD and ACVD.

Gender differences in the effect of visual sexual stimulation on the perceived covariation between freedom and responsibility.

PubMed

Nevala, James D; Gray, Nicholas J; McGahan, Joseph R; Minchew, Teresa

2006-03-01

The authors replicated and extended a test of Epstein's cognitive-experiential self-theory (CEST; S. Epstein, 1973, 1980, 1985, 1994, 2003) regarding subjective estimates of the relationship between freedom and responsibility. CEST predicts that information in the form of sexually provocative images is likely to be processed by the experiential system. The authors' hypothesis was that such experiential processing would cause an increase in the likelihood of participants endorsing as true a statement that proposed a negative correlation between freedom and responsibility. University students (N = 97) in introductory psychology classes viewed 25 images of either men or women in provocative clothing, or a control consisting of academic journal covers, after which they responded to 24 statements proposing either a positive, negative, or noncontingent relationship between freedom and responsibility. Judgments were analyzed according to perceiver gender and target gender, as well as the framing of the proposition and its contingency category. The hypothesis was supported for the men and to a lesser extent for the women. Although priming the experiential system by exposing participants to sexually provocative images did not change endorsement rates of positive contingencies, it did lead to an increase in the likelihood of simultaneously endorsing negative contingencies.

Provocative Questions in Cancer: NCI Seminar

Cancer.gov

science writers' seminar to discuss various aspects of one of NCI’s signature efforts -- the Provocative Questions project. Discussion will focus on the scientific research that surrounds some of these questions.

Occupational asthma due to polyethylene shrink wrapping (paper wrapper's asthma).

PubMed Central

Gannon, P F; Burge, P S; Benfield, G F

1992-01-01

Occupational asthma due to the pyrolysis products of polyvinyl chloride (PVC) produced by shrink wrapping processes has previously been reported. The first case of occupational asthma in a shrink wrap worker using a different plastic, polyethylene, is reported; the association was confirmed by specific bronchial provocation testing. PMID:1440477

Do You Have to be Angry to be Aggressive?

ERIC Educational Resources Information Center

Wienir, Paul L.

Seven hypotheses regarding the role of anger for aggressive behavior were testes in an experimental exchange situation using male children as subjects. In previous studies, anger had not actually been employed as the intervening variable in a provocation/aggressive cue-aggression model. The results indicate a strong relationship between…

Short-term nutritional folate deficiency in rats has a greater effect on choline and acetylcholine metabolism in the peripheral nervous system than in the brain, and this effect escalates with age

PubMed Central

Crivello, Natalia A.; Blusztajn, Jan K.; Joseph, James A.; Shukitt-Hale, Barbara; Smith, Donald E.

2010-01-01

The hypothesis of this study is that a folate-deficient diet (FD) has a greater effect on cholinergic system in the peripheral nervous system than in the brain, and that this effect escalates with age. It was tested by comparing choline and acetylcholine levels in male Sprague Dawley rats fed either control or folate-deficient diets for 10 weeks, starting at age 4 weeks (the young group) or 9 months (the adult group). FD consumption resulted in depletion of plasma folate in both age groups. In young folate-deficient rats, liver and lung choline levels were significantly lower than those in the respective controls. No other significant effects of FD on choline and acetylcholine metabolism were found in young rats. In adult rats, FD consumption markedly decreased choline levels in the liver, kidneys, and heart; furthermore, choline levels in the cortex and striatum were moderately elevated, although hippocampal choline levels were not affected. Acetylcholine levels were higher in the heart, cortex, and striatum but lower in the hippocampus in adult folate-deficient rats, as compared to controls. Higher acetylcholine levels in the striatum in adult folate-deficient rats were also associated with higher dopamine release in the striatal slices. Thus, both age groups showed higher cholinergic metabolic sensitivity to FD in the peripheral nervous system than in the brain. However, compensatory abilities appeared to be better in the young group, implicating the adult group as a preferred model for further investigation of folate-choline-acetylcholine interactions and their role in brain plasticity and cognitive functions. PMID:21056288

Short-term nutritional folate deficiency in rats has a greater effect on choline and acetylcholine metabolism in the peripheral nervous system than in the brain, and this effect escalates with age.

PubMed

Crivello, Natalia A; Blusztajn, Jan K; Joseph, James A; Shukitt-Hale, Barbara; Smith, Donald E

2010-10-01

The hypothesis of this study is that a folate-deficient diet (FD) has a greater effect on cholinergic system in the peripheral nervous system than in the brain, and that this effect escalates with age. It was tested by comparing choline and acetylcholine levels in male Sprague Dawley rats fed either control or folate-deficient diets for 10 weeks, starting at age 4 weeks (the young group) or 9 months (the adult group). Folate-deficient diet consumption resulted in depletion of plasma folate in both age groups. In young folate-deficient rats, liver and lung choline levels were significantly lower than those in the respective controls. No other significant effects of FD on choline and acetylcholine metabolism were found in young rats. In adult rats, FD consumption markedly decreased choline levels in the liver, kidneys, and heart; furthermore, choline levels in the cortex and striatum were moderately elevated, although hippocampal choline levels were not affected. Acetylcholine levels were higher in the heart, cortex, and striatum but lower in the hippocampus in adult folate-deficient rats, as compared to controls. Higher acetylcholine levels in the striatum in adult folate-deficient rats were also associated with higher dopamine release in the striatal slices. Thus, both age groups showed higher cholinergic metabolic sensitivity to FD in the peripheral nervous system than in the brain. However, compensatory abilities appeared to be better in the young group, implicating the adult group as a preferred model for further investigation of folate-choline-acetylcholine interactions and their role in brain plasticity and cognitive functions. Copyright © 2010 Elsevier Inc. All rights reserved.

A novel muscarinic receptor-independent mechanism of KCNQ2/3 potassium channel blockade by Oxotremorine-M.

PubMed

Zwart, Ruud; Reed, Hannah; Clarke, Sophie; Sher, Emanuele

2016-11-15

Inhibition of KCNQ (Kv7) potassium channels by activation of muscarinic acetylcholine receptors has been well established, and the ion currents through these channels have been long known as M-currents. We found that this cross-talk can be reconstituted in Xenopus oocytes by co-transfection of human recombinant muscarinic M1 receptors and KCNQ2/3 potassium channels. Application of the muscarinic acetylcholine receptor agonist Oxotremorine-methiodide (Oxo-M) between voltage pulses to activate KCNQ2/3 channels caused inhibition of the subsequent KCNQ2/3 responses. This effect of Oxo-M was blocked by the muscarinic acetylcholine receptor antagonist atropine. We also found that KCNQ2/3 currents were inhibited when Oxo-M was applied during an ongoing KCNQ2/3 response, an effect that was not blocked by atropine, suggesting that Oxo-M inhibits KCNQ2/3 channels directly. Indeed, also in oocytes that were transfected with only KCNQ2/3 channels, but not with muscarinic M1 receptors, Oxo-M inhibited the KCNQ2/3 response. These results show that besides the usual muscarinic acetylcholine receptor-mediated inhibition, Oxo-M also inhibits KCNQ2/3 channels by a direct mechanism. We subsequently tested xanomeline, which is a chemically distinct muscarinic acetylcholine receptor agonist, and oxotremorine, which is a close analogue of Oxo-M. Both compounds inhibited KCNQ2/3 currents via activation of M1 muscarinic acetylcholine receptors but, in contrast to Oxo-M, they did not directly inhibit KCNQ2/3 channels. Xanomeline and oxotremorine do not contain a positively charged trimethylammonium moiety that is present in Oxo-M, suggesting that such a charged moiety could be a crucial component mediating this newly described direct inhibition of KCNQ2/3 channels. Copyright © 2016 Elsevier B.V. All rights reserved.

Diagnostic tools for post-gastric bypass hypoglycaemia.

PubMed

Emous, M; Ubels, F L; van Beek, A P

2015-10-01

In spite of its evident success, several late complications can occur after gastric bypass surgery. One of these is post-gastric bypass hypoglycaemia. No evidence-based guidelines exist in the literature on how to confirm the presence of this syndrome. This study aims to describe and compare the tests aimed at making a diagnosis of post-gastric bypass hypoglycaemia and to provide a diagnostic approach based upon the available evidence. A search was conducted in PubMed, Cochrane and Embase. A few questionnaires have been developed to measure the severity of symptoms in post-gastric bypass hypoglycaemia but none has been validated. The gold standard for provocation of a hypoglycaemic event is the oral glucose tolerance test or the liquid mixed meal tolerance test. Both show a high prevalence of hypoglycaemia in post-gastric bypass patients with and without hypoglycaemic complaints as well as in healthy volunteers. No uniformly established cut-off values for glucose concentrations are defined in the literature for the diagnosis of post-gastric bypass hypoglycaemia. For establishing an accurate diagnosis of post-gastric bypass hypoglycaemia, a validated questionnaire, in connection with the diagnostic performance of provocation tests, is the most important thing missing. Given these shortcomings, we provide recommendations based upon the current literature. © 2015 World Obesity.

Facilitation of learning and modulation of frontal cortex acetylcholine by ventral pallidal injection of heparin glucosaminoglycan.

PubMed

De Souza Silva, M A; Jezek, K; Weth, K; Müller, H W; Huston, J P; Brandao, M L; Hasenöhrl, R U

2002-01-01

We examined the effects of heparin on learning and frontal cortex acetylcholine parameters following injection of the glucosaminoglycan into the ventral pallidum. In Experiment 1, possible mnemoactive effects of intrapallidal heparin injection were assessed. Rats with chronically implanted cannulae were administered heparin (0.1, 1.0, 10 ng) or vehicle (0.5 microl) and were tested on a one-trial step-through avoidance task. Two retention tests were carried out in each animal, one at 1.5 h after training to measure short-term memory and another at 24 h to measure long-term memory. Post-trial intrapallidal injection of 1.0 ng heparin improved both short- and long-term retention of the task, whereas the lower and the higher dose of the glucosaminoglycan had no effect. When the effective dose of heparin was injected 5 h, rather than immediately after training, it no longer facilitated long-term retention of the conditioned avoidance response. In Experiment 2, the effects of ventral pallidal heparin injection on frontal cortex acetylcholine and choline concentrations were investigated with in vivo microdialysis in anaesthetized rats. Heparin, administered in the dose of 1.0 ng, which was effective in facilitating avoidance performance, produced a delayed increase in cortical acetylcholine levels ipsi- and contralaterally to the side of intrabasalis injection, resembling the known neurochemical effects obtained for another glycosaminoglycan, chondroitin sulfate, which recently was shown to facilitate inhibitory avoidance learning and to increase frontal cortex acetylcholine. The present findings indicate that heparin, like other extracellular matrix proteoglycans, can exert beneficial effects on memory and strengthen the presumptive relationship between such promnestic effects of proteoglycans and basal forebrain cholinergic mechanisms. The data are discussed with respect to the presumed roles of matrix molecules in extrasynaptic volume transmission and in the 'cross-talk' between synapses.

Dysfunctional penile cholinergic nerves in diabetic impotent men

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blanco, R.; Saenz de Tejada, I.; Goldstein, I.

1990-08-01

Impotence in the diabetic man may be secondary to a neuropathic condition of the autonomic penile nerves. The relationship between autonomic neuropathy and impotence in diabetes was studied in human corporeal tissue obtained during implantation of a penile prosthesis in 19 impotent diabetic and 15 nondiabetic patients. The functional status of penile cholinergic nerves was assessed by determining their ability to accumulate tritiated choline (34), and synthesize (34) and release (19) tritiated-acetylcholine after incubation of corporeal tissue with tritiated-choline (34). Tritiated-choline accumulation, and tritiated-acetylcholine synthesis and release were significantly reduced in the corporeal tissue from diabetic patients compared to thatmore » from nondiabetic patients (p less than 0.05). The impairment in acetylcholine synthesis worsened with the duration of diabetes (p less than 0.025). No differences in the parameters measured were found between insulin-dependent (11) and noninsulin-dependent (8) diabetic patients. The ability of the cholinergic nerves to synthesize acetylcholine could not be predicted clinically with sensory vibration perception threshold testing. It is concluded that there is a functional penile neuropathic condition of the cholinergic nerves in the corpus cavernosum of diabetic impotent patients that may be responsible for the erectile dysfunction.« less

391 Description of Drug Allergy Study Conducted in a Teaching Hospital between October 2007 and March 2011

PubMed Central

Rodríguez Martínez, Consuelo Fernanda; Rubio, Alicia Sciaraffia

2012-01-01

Background The World Allergy Organization (WAO) in 2003 defined ‘drug allergy’ as an immunologically mediated drug hypersensitivity reaction. The mechanism of drug allergy may be either IgE or non-IgE mediated. The true incidence of drug allergy is not known. There are only few studies/datasets using standardized clinical questionnaires and validated in vivo or in vitro tests to confirm the diagnosis of drug allergy. Here we have analyzed the obtained results of in vivo test in suspected drug allergy patients. Methods Data from the Centre of Allergies of the Clinical Hospital of the Universidad de Chile between the months of October 2007 and March 2011 was obtained. The information of the protocols of drug executed, by defining as Protocol the study of a probable allergy by 2 or more procedures, which can be: Prick Test, intradermal reaction, specific IgE and/or Test Patch. Results For a total of 126 drug protocols, 25% of them were trivírica vaccine, 24% β-lactams, 21% local anaesthetics and 10% to general anesthesia (inductors, muscle relaxants and Latex). Of the total of patients undergoing protocols the most of them were women, there is no clear difference between the number of children and adults. The temporal distribution of protocols was stable between the months of October 2007 and March 2009 (15 protocols/semester), to then become variable, reaching values between 10 and 29 every 6 months. Of total protocols, 30.1% were positive; only one patient presented a mild adverse reaction (local welt). The β-lactams being most often the positive drugs. Protocols involving pethidine 100% was positive, diclofenac 33%, dipyrone, ketoprofen and hydrocortisone each one 25%. The most accomplished protocol was trivírica vaccine, resulting in 100% negative. Of all negative protocols 58% went to provocation, resulting in a 8% positive, including one provocation to the trívirica vaccine. Conclusions Methodologicall study is very important for a possible drug allergy, because history is not enough to certify the diagnosis. To do a provocation test to a negative protocol is crucial.

Determination of picomole quantities of acetylcholine and choline in physiologic salt solutions.

PubMed

Gilberstadt, M L; Russell, J A

1984-04-01

An assay capable of detecting tens-of-picomole quantities of choline and acetylcholine in milliliter volumes of a physiological salt solution has been developed. Silica column chromatography was used to bind and separate 10-3000 pmol [14C]choline and [14C]acetylcholine standards made up in 3 ml of a bicarbonate-buffered Krebs-Ringer solution. The silica columns bound 95-98% of both choline and acetylcholine. Of the bound choline 84-87% was eluted in 1.5 ml of 0.075 N HCl, whereas 95-98% of the bound acetylcholine was eluted in a subsequent wash with 1.5 ml of 0.030 N HCl in 10% 2-butanone. Vacuum centrifugation of the eluants yielded small white pellets with losses of choline and acetylcholine of only 1%. Dried pellets of unlabeled choline and acetylcholine standards were assayed radioenzymatically using [gamma-32P]ATP, choline kinase, and acetylcholinesterase. The net disintegrations per minute of choline[32P]phosphate product was proportional to both the acetylcholine (10-3000 pmol) and choline (30-3000 pmol) standards. The "limit sensitivity" was 8.5 pmol for acetylcholine and 11.4 pmol for choline. Cross-contamination of the choline assay by acetylcholine averaged 1.3%, whereas contamination of the acetylcholine assay by choline averaged 3.1%.

Synthesis, in vitro and in vivo studies, and molecular modeling of N-alkylated dextromethorphan derivatives as non-competitive inhibitors of α3β4 nicotinic acetylcholine receptor.

PubMed

Jozwiak, Krzysztof; Targowska-Duda, Katarzyna M; Kaczor, Agnieszka A; Kozak, Joanna; Ligeza, Agnieszka; Szacon, Elzbieta; Wrobel, Tomasz M; Budzynska, Barbara; Biala, Grazyna; Fornal, Emilia; Poso, Antti; Wainer, Irving W; Matosiuk, Dariusz

2014-12-15

9 N-alkylated derivatives of dextromethorphan are synthesized and studied as non-competitive inhibitors of α3β4 nicotinic acetylcholine receptors (nAChRs). In vitro activity towards α3β4 nicotinic acetylcholine receptor is determined using a patch-clamp technique and is in the micromolar range. Homology modeling, molecular docking and molecular dynamics of ligand-receptor complexes in POPC membrane are used to find the mode of interactions of N-alkylated dextromethorphan derivatives with α3β4 nAChR. The compounds, similarly as dextromethorphan, interact with the middle portion of α3β4 nAChR ion channel. Finally, behavioral tests confirmed potential application of the studied compounds for the treatment of addiction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Influence of tilt training on activation of the autonomic nervous system in patients with vasovagal syncope.

PubMed

Gajek, Jacek; Zyśko, Dorota; Halawa, Bogumił; Mazurek, Walentyna

2006-04-01

Tilt training is a new treatment for vasovagal syncope. Its therapeutic efficacy is thought to be the result of the desensitization of cardiopulmonary receptors, but it could be the influence of the tilt training on the activation of the autonomic nervous system as well. The study group consisted of 24 vasovagal patients (17 women and 7 men) aged 32.5 +/- 11.8 years. The diagnostic head-up tilt test was performed according to the Italian protocol with nitroglycerin if necessary. The monitoring head-up tilt test was performed according to the Westminster protocol without provocation, after 1 to 3 months of tilt training. Holter ECG recordings for HRV parameters (time and frequency domain) were obtained from selected 2-min intervals before, during and after the diagnostic and monitoring tilt test. The diagnostic test was positive in the passive phase in 6 and after provocation in 18 patients. During the training period no syncope occurred. Analysing the HRV parameters we demonstrated the following findings: I. mRR decreases immediately after assumption of a vertical position in both tests (diagnostic and monitoring) but in the diagnostic test its further decrease occurs earlier than in the monitoring test; 2. the absolute power of the HF component is greater in the early phase of tilt after tilt training than in the corresponding period in the diagnostic test. After a longer period of tilt training the activation of the sympathetic nervous system in response to the erect position is diminished.

Effect of N-acetylcysteine on vascular endothelium function in aorta from oophorectomized rats.

PubMed

Delgado, J L; Landeras, J; Carbonell, L F; Parilla, J J; Abad, L; Quesada, T; Fiol, G; Hernández, I

1999-01-01

1. Experiments were performed to examine and to compare vascular endothelial function in aortic rings from oophorectomized and from ovary-intact rats and to test the effect of thiol compound as N-acetylcysteine on endothelial function. 2. In precontracted aortic rings from oophorectomized and intact rats, vascular endothelial function was evaluated by measuring changes in isometric force in response to cumulative doses of superoxide dismutase, acetylcholine and sodium nitroprusside. 3. In studies designed to assess the tone-related release of nitric oxide from aortic rings moderately precontracted with phenylephrine, superoxide dismutase produced a lower concentration-related relaxant response in aortic rings from oophorectomized rats than from ovary intact rats. 4. Acetylcholine caused a concentration- and endothelium-dependent relaxation of less magnitude in aortic rings from oophorectomized animals compared with those from ovary-intact rats. Addition of N-omega-nitro-L-arginine methyl ester eliminated the relaxation induced by both superoxide dismutase and acetylcholine. 5. No differences between groups were noticed in the concentration-relaxation curve induced by sodium nitroprusside. 6. Preincubation with N-acetylcysteine normalized the depressed vasorelaxant response to acetylcholine in the aortic rings from oophorectomized rats, whereas the concentration-response curve for acetylcholine in aortic rings from ovary-intact rats did not alter. 7. These results suggest that the absence of ovary estrogens is associated with a vascular endothelium dysfunction that can be reverted by addition of N-acetylcysteine, a thiol-containing compound with a free radical scavenger effect.

Effects on skin blood flow by provocation during local analgesia.

PubMed

Arildsson, M; Nilsson, G E; Strömberg, T

2000-01-01

Although topical analgesia cream has been used for several years, little is known about its effects on the microcirculation. Previous studies have shown a vasoconstrictive effect after short application times and a vasodilatation after longer application. It has also been shown that vasomotion does not occur in the analgesized skin. The present study was undertaken to investigate the alterations in skin blood perfusion following local cooling, local heating and pin-pricking after the establishment of analgesia. In 11 healthy volunteers, skin analgesia was attained by use of a eutectic mixture of lidocaine and prilocaine (EMLA, Astra Pain Control AB, Sweden) applied to the skin three hours prior to provocation. The changes in skin blood perfusion, after applying three different provocation methods, were studied using the laser Doppler technique. Local cooling and heating to temperatures of +10 and +45 degrees C, respectively, were applied for 9 s by use of a copper probe (O12 mm). In the pin-prick provocation method, a combined effect of deflection and penetration of the skin to in total 3 mm was attained. Identical provocation methods were applied to placebo treated and untreated skin areas. After heat provocation, significant differences in the perfusion response between the treatments were seen (P < 0.0001). Skin areas treated with analgesia cream responded with a slow increase in perfusion that persisted beyond the four minute measurement period. Placebo and untreated areas decreased their perfusion over time. After cooling a significant reduction in skin perfusion was seen, irrespective of the treatment. Similarly, after pin-pricking a perfusion increase was seen for all treatments. The findings indicate that topical analgesia influences the myogenic control of the blood flow in those vascular plexa measured by laser Doppler following heat provocation. No differences could be seen in the response to pin-pricking and cooling for the different treatments. Copyright 2000 Academic Press.

Face-Emotion Processing in Offspring at Risk for Panic Disorder.

ERIC Educational Resources Information Center

Pine, Daniel S.; Klein, Rachel G.; Mannuzza, Salvatore; Moulton, John L., III; Lissek, Shmuel; Guardino, Mary; Woldehawariat, Girma

2005-01-01

Objective: Panic disorder (PD) has been linked to perturbed processing of threats. This study tested the hypotheses that offspring of parents with PD and offspring with anxiety disorders display relatively greater sensitivity and attention allocation to fear provocation. Method: Offspring of adults with PD, major depressive disorder (MDD), or no…

Rapid Detection of Visually Provocative Animals by Preschool Children and Adults

ERIC Educational Resources Information Center

Penkunas, Michael J.; Coss, Richard G.

2013-01-01

The ability to detect dangerous animals rapidly in complex landscapes has been historically important during human evolution. Previous research has shown that snake images are more readily detected than images of benign animals. To provide a stringent test of superior snake detection in preschool children and adults, Experiment 1 consisted of two…

Endoplasmic reticulum stress contributes to acetylcholine receptor degradation by promoting endocytosis in skeletal muscle cells.

PubMed

Du, Ailian; Huang, Shiqian; Zhao, Xiaonan; Zhang, Yun; Zhu, Lixun; Ding, Ji; Xu, Congfeng

2016-01-15

After binding by acetylcholine released from a motor neuron, a nicotinic acetylcholine receptor at the neuromuscular junction produces a localized end-plate potential, which leads to muscle contraction. Improper turnover and renewal of acetylcholine receptors contributes to the pathogenesis of myasthenia gravis. In the present study, we demonstrate that endoplasmic reticulum (ER) stress contributes to acetylcholine receptor degradation in C2C12 myocytes. We further show that ER stress promotes acetylcholine receptor endocytosis and lysosomal degradation, which was dampened by blocking endocytosis or treating with lysosome inhibitor. Knockdown of ER stress proteins inhibited acetylcholine receptor endocytosis and degradation, while rescue assay restored its endocytosis and degradation, confirming the effects of ER stress on promoting endocytosis-mediated degradation of junction acetylcholine receptors. Thus, our studies identify ER stress as a factor promoting acetylcholine receptor degradation through accelerating endocytosis in muscle cells. Blocking ER stress and/or endocytosis might provide a novel therapeutic approach for myasthenia gravis. Copyright © 2015 Elsevier B.V. All rights reserved.

Growth hormone: its measurement and the need for assay harmonization.

PubMed

Wood, P

2001-09-01

Serum human growth hormone (hGH) assays show a wide range in bias and in cut-off values for provocative tests, which vary from 13.5 to 35-40 mU/L when they have been established. Studies using novel hGH assays show that methods that are absolutely specific for 22-kDa hGH may not identify bioactive hGH peaks and that 20:22-kDa hGH ratios are increased in acromegaly. Greater harmonization of serum hGH methods can be achieved by: changing from IS 80/505 to IS 98/574, which is calibrated in mass units of recombinant 22-kDa hGH; using monoclonal/polyclonal or polyclonal/polyclonal antibody combinations that measure both 20-kDa and 22-kDa hGH; the development of assays such as the immunofunctional hGH assay which has the convenience of an immunometric assay but gives results that correlate better with bioassays collaboration between manufacturers and laboratories to establish method-related cut-off limits for provocative tests of hGH status.

Domestic Violence and Vagal Reactivity to Peer Provocation

PubMed Central

Katz, Lynn Fainsilber

2007-01-01

This paper examined whether individual differences in children’s vagal reactivity to peer provocation was related to domestic violence within the family. It also examined the question of whether conduct-problem children who show vagal augmentation to peer provocation come from families with high levels of domestic violence. During the peer provocation, children were expecting to interact with a difficult peer while vagal reactivity was assessed. Groups were divided into children who showed vagal augmentation and vagal suppression to the stressful peer interaction. Findings indicated that conduct-problem children who showed vagal augmentation to interpersonal challenge came from families with the highest levels of domestic violence. Vagal augmentation was also associated with a greater number of conduct-related problems for those children exposed to high levels of domestic violence. Discussion highlights the role of individual differences in physiological reactivity in understanding children’s behavior problems in relation to domestic violence. PMID:17118516

Perpetrators and targets of bullying at work: role stress and individual differences.

PubMed

Matthiesen, Stig Berge; Einarsen, Ståle

2007-01-01

A workplace survey study (N = 2215, response rate 47%) revealed that about 16% of the sample may be categorized as either perpetrators (5.4%), provocative victims (2.1%), or as targets of bullying (8.3%). Targets of bullying, provocative victims, and bullies were compared with those 84% who do not report any involvement with respect to bullying at work, self-esteem, aggressive tendencies, prior experiences of bullying, or experiences of role stress. Perpetrators were found to have a higher level of aggression than did the comparison group and the targets. Provocative victims manifested a low level of self-esteem and social competency combined with a high level of aggressiveness. Targets of bullying revealed low levels of self-esteem and social competency. Targets, provocative victims, and perpetrators reported elevated levels of role stress in the form of unclear or conflicting demands and expectations around work tasks and daily work.

alpha 4 beta 2 subunit combination specific pharmacology of neuronal nicotinic acetylcholine receptors in N1E-115 neuroblastoma cells.

PubMed

Zwart, R; Abraham, D; Oortgiesen, M; Vijverberg, H P

1994-08-22

Pharmacological characteristics of native neuronal nicotinic acetylcholine receptor-mediated ion currents in mouse N1E-115 neuroblastoma cells have been investigated by superfusion of voltage clamped cells with known concentrations of the agonists acetylcholine, nicotine and cytisine, and the antagonists alpha-bungarotoxin and neuronal bungarotoxin. The sensitivity of the nicotinic acetylcholine receptor for agonists followed the agonist potency rank-order: nicotine approximately acetylcholine > cytisine. The EC50 values of acetylcholine and nicotine are 78 microM and 76 microM, respectively. Equal concentrations of acetylcholine and nicotine induce inward currents with approximately the same peak amplitude whereas cytisine induces much smaller inward currents. Acetylcholine-induced currents are unaffected by high concentrations of alpha-bungarotoxin. Conversely, at 10 and 90 nM neuronal bungarotoxin reduces the amplitude of the 1 mM acetylcholine-induced inward current to 47% and 11% of control values, respectively. Both the agonist potency rank-order and the differential sensitivity to snake toxins of nicotinic receptors in N1E-115 cells are consistent with the known pharmacological profile of alpha 4 beta 2 nicotinic receptors expressed in Xenopus oocytes and distinct from those of all other nicotinic acetylcholine receptors of known functional subunit compositions. All data indicate that the native nicotinic acetylcholine receptor in N1E-115 cells is an assembly of alpha 4 and beta 2 subunits, the putative major subtype of nicotinic acetylcholine receptor in the brain.

Axon Response to Guidance Cues Is Stimulated by Acetylcholine in Caenorhabditis elegans

PubMed Central

Xu, Yan; Ren, Xing-Cong; Quinn, Christopher C.; Wadsworth, William G.

2011-01-01

Gradients of acetylcholine can stimulate growth cone turning when applied to neurons grown in culture, and it has been suggested that acetylcholine could act as a guidance cue. However, the role acetylcholine plays in directing axon migrations in vivo is not clear. Here, we show that acetylcholine positively regulates signaling pathways that mediate axon responses to guidance cues in Caenorhabditis elegans. Mutations that disrupt acetylcholine synthesis, transportation, and secretion affect circumferential axon guidance of the AVM neuron and in these mutants exogenously supplied acetylcholine improves AVM circumferential axon guidance. These effects are not observed for the circumferential guidance of the DD and VD motor neuron axons, which are neighbors of the AVM axon. Circumferential guidance is directed by the UNC-6 (netrin) and SLT-1 (slit) extracellular cues, and exogenously supplied acetylcholine can improve AVM axon guidance in mutants when either UNC-6– or SLT-1–induced signaling is disrupted, but not when both signaling pathways are perturbed. Not in any of the mutants does exogenously supplied acetylcholine improve DD and VD axon guidance. The ability of acetylcholine to enhance AVM axon guidance only in the presence of either UNC-6 or SLT-1 indicates that acetylcholine potentiates UNC-6 and SLT-1 guidance activity, rather than acting itself as a guidance cue. Together, our results show that for specific neurons acetylcholine plays an important role in vivo as a modulator of axon responses to guidance cues. PMID:21868605

Comparison of (/sup 3/H)nicotine and (/sup 3/H)acetylcholine binding in mouse brain: regional distribution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sershen, H.; Reith, M.E.; Hashim, A.

1985-06-01

In a continuing study of nicotine binding sites, the authors determined the relative amount of nicotine binding and acetylcholine binding in various brain regions of C57/BL and of DBA mice. Although midbrain showed the highest and cerebellum the lowest binding for both (/sup 3/H)nicotine and (/sup 3/H)acetylcholine, the ratio of nicotine to acetylcholine binding showed a three-fold regional variation. Acetylcholine inhibition of (/sup 3/H)nicotine binding indicated that a portion of nicotine binding was not inhibited by acetylcholine. These results indicate important differences between the binding of (+/-)-(/sup 3/H)nicotine and that of (/sup 3/H)acetylcholine.

Beta-phenylethylamine stimulates striatal acetylcholine release through activation of the AMPA glutamatergic pathway.

PubMed

Ishida, Kota; Murata, Mikio; Kato, Masatoshi; Utsunomiya, Iku; Hoshi, Keiko; Taguchi, Kyoji

2005-09-01

Using an in vivo intra-striatal microdialysis technique, we examined the effects of systemically administered beta-phenylethylamine (beta-PEA), a psychomotor stimulating trace amine, on striatal acetylcholine release in freely moving rats. Infusion of N-methyl-D-aspartic acid (NMDA; 10(-5) M) significantly increased acetylcholine release. In addition, locally applied amino-3-hydroxy-5-methylisozasole-4-propionic acid (AMPA; 10(-5) M) significantly increased acetylcholine release in the striatum. Intra-striatal application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10(-5) M), an AMPA-type glutamatergic receptor antagonist, had little effect on acetylcholine release, while application of MK-801 (10(-5) M, 10(-6) M), an NMDA-type glutamatergic receptor antagonist, significantly reduced acetylcholine release. Acetylcholine within striatal perfusate was significantly increased by intraperitoneal administration of beta-PEA in a dose-dependent manner. This increase in acetylcholine release was completely blocked by application of CNQX (10(-5) M) through the microdialysis probe into the striatum. However, increased acetylcholine response to systemic beta-PEA was unaltered by addition of MK-801 to the perfusion medium. These results suggest a regulatory function of beta-PEA, mediated by AMPA-type glutamatergic receptors, on the release of acetylcholine in the rat striatum.

Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model.

PubMed

Rajendran, Ranjith; Borghi, Elisa; Falleni, Monica; Perdoni, Federica; Tosi, Delfina; Lappin, David F; O'Donnell, Lindsay; Greetham, Darren; Ramage, Gordon; Nile, Christopher

2015-08-01

Both neuronal acetylcholine and nonneuronal acetylcholine have been demonstrated to modulate inflammatory responses. Studies investigating the role of acetylcholine in the pathogenesis of bacterial infections have revealed contradictory findings with regard to disease outcome. At present, the role of acetylcholine in the pathogenesis of fungal infections is unknown. Therefore, the aim of this study was to determine whether acetylcholine plays a role in fungal biofilm formation and the pathogenesis of Candida albicans infection. The effect of acetylcholine on C. albicans biofilm formation and metabolism in vitro was assessed using a crystal violet assay and phenotypic microarray analysis. Its effect on the outcome of a C. albicans infection, fungal burden, and biofilm formation were investigated in vivo using a Galleria mellonella infection model. In addition, its effect on modulation of host immunity to C. albicans infection was also determined in vivo using hemocyte counts, cytospin analysis, larval histology, lysozyme assays, hemolytic assays, and real-time PCR. Acetylcholine was shown to have the ability to inhibit C. albicans biofilm formation in vitro and in vivo. In addition, acetylcholine protected G. mellonella larvae from C. albicans infection mortality. The in vivo protection occurred through acetylcholine enhancing the function of hemocytes while at the same time inhibiting C. albicans biofilm formation. Furthermore, acetylcholine also inhibited inflammation-induced damage to internal organs. This is the first demonstration of a role for acetylcholine in protection against fungal infections, in addition to being the first report that this molecule can inhibit C. albicans biofilm formation. Therefore, acetylcholine has the capacity to modulate complex host-fungal interactions and plays a role in dictating the pathogenesis of fungal infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

In vivo release of non-neuronal acetylcholine from the human skin as measured by dermal microdialysis: effect of botulinum toxin

PubMed Central

Schlereth, Tanja; Birklein, Frank; Haack, Katrin an; Schiffmann, Susanne; Kilbinger, Heinz; Kirkpatrick, Charles James; Wessler, Ignaz

2005-01-01

Acetylcholine is synthesized in the majority of non-neuronal cells, for example in human skin. In the present experiments, the in vivo release of acetylcholine was measured by dermal microdialysis. Two microdialysis membranes were inserted intradermally at the medial shank of volunteers. Physiological saline containing 1 μM neostigmine was perfused at a constant rate of 4 μl min−1 and the effluent was collected in six subsequent 20 min periods. Acetylcholine was measured by high-pressure liquid chromatography (HPLC) combined with bioreactors and electrochemical detection. Analysis of the effluent by HPLC showed an acetylcholine peak that disappeared, when the analytical column was packed with acetylcholine-specific esterase, confirming the presence of acetylcholine. In the absence of neostigmine, 71±51 pmol acetylcholine (n=4) was found during a 120 min period. The amount increased to 183±43 pmol (n=34), when the perfusion medium contained 1 μM neostigmine. Injection of 100 MU botulinum toxin subcutaneously blocked sweating completely, but the release of acetylcholine was not affected (botulinum toxin treated skin: 116±70 pmol acetylcholine/120 min; untreated skin: 50±20 pmol; n=4). Quinine (1 mM), inhibitor of organic cation transporters, and carnitine (0.1 mM), substrate of the Na+-dependent carnitine transporter OCTN2, tended to reduce acetylcholine release (by 40%, not significant). Our experiments demonstrate, for the first time, the in vivo release of non-neuronal acetylcholine in human skin. Organic cation transporters are not predominantly involved in the release of non-neuronal acetylcholine from the human skin. PMID:16273117

Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model

PubMed Central

Rajendran, Ranjith; Borghi, Elisa; Falleni, Monica; Perdoni, Federica; Tosi, Delfina; Lappin, David F.; O'Donnell, Lindsay; Greetham, Darren; Ramage, Gordon

2015-01-01

Both neuronal acetylcholine and nonneuronal acetylcholine have been demonstrated to modulate inflammatory responses. Studies investigating the role of acetylcholine in the pathogenesis of bacterial infections have revealed contradictory findings with regard to disease outcome. At present, the role of acetylcholine in the pathogenesis of fungal infections is unknown. Therefore, the aim of this study was to determine whether acetylcholine plays a role in fungal biofilm formation and the pathogenesis of Candida albicans infection. The effect of acetylcholine on C. albicans biofilm formation and metabolism in vitro was assessed using a crystal violet assay and phenotypic microarray analysis. Its effect on the outcome of a C. albicans infection, fungal burden, and biofilm formation were investigated in vivo using a Galleria mellonella infection model. In addition, its effect on modulation of host immunity to C. albicans infection was also determined in vivo using hemocyte counts, cytospin analysis, larval histology, lysozyme assays, hemolytic assays, and real-time PCR. Acetylcholine was shown to have the ability to inhibit C. albicans biofilm formation in vitro and in vivo. In addition, acetylcholine protected G. mellonella larvae from C. albicans infection mortality. The in vivo protection occurred through acetylcholine enhancing the function of hemocytes while at the same time inhibiting C. albicans biofilm formation. Furthermore, acetylcholine also inhibited inflammation-induced damage to internal organs. This is the first demonstration of a role for acetylcholine in protection against fungal infections, in addition to being the first report that this molecule can inhibit C. albicans biofilm formation. Therefore, acetylcholine has the capacity to modulate complex host-fungal interactions and plays a role in dictating the pathogenesis of fungal infections. PMID:26092919

Clinical tube weaning supported by hunger provocation in fully-tube-fed children.

PubMed

Hartdorff, Caroline M; Kneepkens, C M Frank; Stok-Akerboom, Anita M; van Dijk-Lokkart, Elisabeth M; Engels, Michelle A H; Kindermann, Angelika

2015-04-01

Children with congenital malformations, mental retardation, and complex early medical history frequently have feeding problems. Although tube feeding is effective in providing the necessary energy and nutrients, it decreases the child's motivation to eat and may lead to oral aversion. In this study, we sought to confirm our previous results, showing that a multidisciplinary clinical hunger provocation program may lead to quick resumption of oral feeding. In a crossover study, 22 children of 9 to 24 months of age who were fully dependent on tube feeding were randomly assigned to one of two groups: group A, intervention group (2-week multidisciplinary clinical hunger provocation program); and group B, control group (4-week outpatient treatment by the same multidisciplinary team). Patients failing one treatment were reassigned to the other treatment group. Primary outcome measures were at least 75% orally fed at the conclusion of the intervention and fully orally fed and gaining weight 6 months after the intervention. In group A, 9/11 patients were successfully weaned from tube feeding (2 failures: 1 developed ulcerative colitis, 1 drop-out). In group B, only 1 patient was weaned successfully; 10/11 were reassigned to the clinical hunger provocation program, all being weaned successfully. Six months after the intervention, 1 patient had to resume tube feeding. In total, in the control group, 1/11 (9%) was weaned successfully as compared with 18/21 (86%) in the hunger provocation group (P < 0.001). Multidisciplinary clinical hunger provocation is an effective short-term intervention for weaning young children from tube feeding.

Do TETRA (Airwave) base station signals have a short-term impact on health and well-being? A randomized double-blind provocation study.

PubMed

Wallace, Denise; Eltiti, Stacy; Ridgewell, Anna; Garner, Kelly; Russo, Riccardo; Sepulveda, Francisco; Walker, Stuart; Quinlan, Terence; Dudley, Sandra; Maung, Sithu; Deeble, Roger; Fox, Elaine

2010-06-01

"Airwave" is the new communication system currently being rolled out across the United Kingdom for the police and emergency services, based on the Terrestrial Trunked Radio Telecommunications System (TETRA). Some police officers have complained about skin rashes, nausea, headaches, and depression as a consequence of using their Airwave handsets. In addition, a small subgroup in the population self-report being sensitive to electromagnetic fields (EMFs) in general. We conducted a randomized double-blind provocation study to establish whether short-term exposure to a TETRA base station signal has an impact on the health and well-being of individuals with self-reported "electrosensitivity" and of participants who served as controls. Fifty-one individuals with self-reported electrosensitivity and 132 age- and sex-matched controls participated in an open provocation test; 48 sensitive and 132 control participants went on to complete double-blind tests in a fully screened semianechoic chamber. Heart rate, skin conductance, and blood pressure readings provided objective indices of short-term physiological response. Visual analog scales and symptom scales provided subjective indices of well-being. We found no differences on any measure between TETRA and sham (no signal) under double-blind conditions for either controls or electrosensitive participants, and neither group could detect the presence of a TETRA signal at rates greater than chance (50%). When conditions were not double blind, however, the self-reported electrosensitive individuals did report feeling worse and experienced more severe symptoms during TETRA compared with sham. Our findings suggest that the adverse symptoms experienced by electrosensitive individuals are due to the belief of harm from TETRA base stations rather than to the low-level EMF exposure itself.

Do TETRA (Airwave) Base Station Signals Have a Short-Term Impact on Health and Well-Being? A Randomized Double-Blind Provocation Study

PubMed Central

Wallace, Denise; Eltiti, Stacy; Ridgewell, Anna; Garner, Kelly; Russo, Riccardo; Sepulveda, Francisco; Walker, Stuart; Quinlan, Terence; Dudley, Sandra; Maung, Sithu; Deeble, Roger; Fox, Elaine

2010-01-01

Background “Airwave” is the new communication system currently being rolled out across the United Kingdom for the police and emergency services, based on the Terrestrial Trunked Radio Telecommunications System (TETRA). Some police officers have complained about skin rashes, nausea, headaches, and depression as a consequence of using their Airwave handsets. In addition, a small subgroup in the population self-report being sensitive to electromagnetic fields (EMFs) in general. Objectives We conducted a randomized double-blind provocation study to establish whether short-term exposure to a TETRA base station signal has an impact on the health and well-being of individuals with self-reported “electrosensitivity” and of participants who served as controls. Methods Fifty-one individuals with self-reported electrosensitivity and 132 age- and sex-matched controls participated in an open provocation test; 48 sensitive and 132 control participants went on to complete double-blind tests in a fully screened semianechoic chamber. Heart rate, skin conductance, and blood pressure readings provided objective indices of short-term physiological response. Visual analog scales and symptom scales provided subjective indices of well-being. Results We found no differences on any measure between TETRA and sham (no signal) under double-blind conditions for either controls or electrosensitive participants, and neither group could detect the presence of a TETRA signal at rates greater than chance (50%). When conditions were not double blind, however, the self-reported electrosensitive individuals did report feeling worse and experienced more severe symptoms during TETRA compared with sham. Conclusions Our findings suggest that the adverse symptoms experienced by electrosensitive individuals are due to the belief of harm from TETRA base stations rather than to the low-level EMF exposure itself. PMID:20075020

An Apparatus to Deliver Mannitol Powder for Bronchial Provocation in Children Under Six Years Old.

PubMed

Tang, Patricia; Leung, Sharon S Y; Hor, Eleanor; Ruzycki, Conor A; Carrigy, Nicholas B; Finlay, Warren H; Brannan, John D; Devadason, Sunalene; Anderson, Sandra D; Sly, Peter D; Samnick, Kevin; Chan, Hak-Kim

2015-12-01

Currently bronchial provocation testing (BPT) using mannitol powder cannot be performed in children under 6 years. A primary reason is it is challenging for children at this age to generate a consistent inspiratory effort to inhale mannitol efficiently from a dry powder inhaler. A prototype system, which does not require any inhalation training from the pediatric subject, is reported here. It uses an external source of compressed air to disperse mannitol powder into a commercial holding chamber. Then the subject uses tidal breathing to inhale the aerosol. The setup consists of a commercially available powder disperser and Volumatic™ holding chamber. Taguchi experimental design was used to identify the effect of dispersion parameters (flow rate of compressed air, time compressed air is applied, mass of powder, and the time between dispersion and inhalation) on the fine particle dose (FPD). The prototype was tested in vitro using a USP throat connected to a next generation impactor. The aerosols from the holding chamber were drawn at 10 L/min. A scaling factor for estimating the provoking dose to induce a 15% reduction in forced expiratory volume in 1 second (FEV1) (PD15) was calculated using anatomical dimensions of the human respiratory tract at various ages combined with known dosing values from the adult BPT. Consistent and doubling FPDs were successfully generated based on the Taguchi experimental design. The FPD was reliable over a range of 0.8 (±0.09) mg to 14 (±0.94) mg. The calculated PD15 for children aged 1-6 years ranged from 7.1-30 mg. The FPDs generated from the proposed set up are lower than the calculated PD15 and therefore are not expected to cause sudden bronchoconstriction. A prototype aerosol delivery system has been developed that is consistently able to deliver doubling doses suitable for bronchial provocation testing in young children.

Pravastatin and endothelium dependent vasomotion after coronary angioplasty: the PREFACE trial.

PubMed

Mulder, H J; Schalij, M J; Kauer, B; Visser, R F; van Dijkman, P R; Jukema, J W; Zwinderman, A H; Bruschke, A V

2001-11-01

To test the hypothesis that the 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor pravastatin ameliorates endothelium mediated responses of dilated coronary segments: the PREFACE (pravastatin related effects following angioplasty on coronary endothelium) trial. A double blind, randomised, placebo controlled, multicentre study. Four hospitals in the Netherlands. 63 non-smoking, non-hypercholesterolaemic patients scheduled for elective balloon angioplasty (pravastatin 34, placebo 29). The effects of three months of pravastatin treatment (40 mg daily) on endothelium dependent vasomotor function were studied. Balloon angioplasty was undertaken one month after randomisation, and coronary vasomotor function tests using acetylcholine were performed two months after balloon angioplasty. The angiograms were analysed quantitatively. The efficacy measure was the acetylcholine induced change in mean arterial diameter, determined in the dilated segment and in an angiographically normal segment of an adjacent non-manipulated coronary artery. Increasing acetylcholine doses produced vasoconstriction in the dilated segments (p = 0.004) but not in the normal segments. Pravastatin did not affect the vascular response to acetylcholine in either the dilated segments (p = 0.09) or the non-dilated sites. Endothelium dependent vasomotion in normal segments was correlated with that in dilated segments (r = 0.47, p < 0.001). There were fewer procedure related events in the pravastatin group than in the placebo group (p < 0.05). Endothelium dependent vasomotion in normal segments is correlated with that in dilated segments. A significant beneficial effect of pravastatin on endothelial function could not be shown, but in the dilated segments there was a trend towards a beneficial treatment effect in the pravastatin group.

Learning and Memory Impairments in a Congenic C57BL/6 Strain of Mice That Lacks the M2 Muscarinic Acetylcholine Receptor Subtype

PubMed Central

Bainbridge, Natalie K.; Koselke, Lisa R.; Jeon, Jongrye; Bailey, Kathleen R.; Wess, Jürgen; Crawley, Jacqueline N.; Wrenn, Craige C.

2009-01-01

The neurotransmitter acetylcholine is an important modulator of cognitive functions including attention, learning, and memory. The actions of acetylcholine are mediated by five distinct muscarinic acetylcholine receptor subtypes (M1-M5). The lack of drugs with a high degree of selectivity for these subtypes has impeded the determination of which subtypes mediate which components of cholinergic neurotransmission relevant to cognitive abilities. The present study examined the behavioral functions of the M2 muscarinic receptor subtype by utilizing congenic C57BL/6 mice possessing a null-mutation in the M2 muscarinic receptor gene (M2−/− mice). Comprehensive assessment of general health and neurological function found no major differences between M2−/− and wild-type (M2+/+) mice. In tests of learning and memory, M2−/− mice were impaired in the acquisition (trials to criterion), but not the retention (72 hr) of a passive avoidance task. In a novel open field, M2−/− mice were impaired in between-sessions, but not within-session habituation. In a holeboard test of spatial memory, M2−/− mice committed more errors in working memory than M2+/+ mice. Reference memory did not differ between the genotypes. M2−/− mice showed no impairments in either cued or contextual fear conditioning. These findings replicate and extend earlier findings in a hybrid strain and solidify the interpretation that the M2 receptor plays a critical role in specific components of cognitive abilities. PMID:18346798

Repeated administration of almonds increases brain acetylcholine levels and enhances memory function in healthy rats while attenuates memory deficits in animal model of amnesia.

PubMed

Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Tabassum, Saiqa; Madiha, Syeda; Rafiq, Sahar; Tariq, Sumayya; Batool, Tuba Sharf; Saleem, Sadia; Naqvi, Fizza; Perveen, Tahira; Haider, Saida

2016-01-01

Dietary nutrients may play a vital role in protecting the brain from age-related memory dysfunction and neurodegenerative diseases. Tree nuts including almonds have shown potential to combat age-associated brain dysfunction. These nuts are an important source of essential nutrients, such as tocopherol, folate, mono- and poly-unsaturated fatty acids, and polyphenols. These components have shown promise as possible dietary supplements to prevent or delay the onset of age-associated cognitive dysfunction. This study investigated possible protective potential of almond against scopolamine induced amnesia in rats. The present study also investigated a role of acetylcholine in almond induced memory enhancement. Rats in test group were orally administrated with almond suspension (400 mg/kg/day) for four weeks. Both control and almond-treated rats were then divided into saline and scopolamine injected groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM) and novel object recognition (NOR) task. Cholinergic function was determined in terms of hippocampal and frontal cortical acetylcholine content and acetylcholinesterase activity. Results of the present study suggest that almond administration for 28 days significantly improved memory retention. This memory enhancing effect of almond was also observed in scopolamine induced amnesia model. Present study also suggests a role of acetylcholine in the attenuation of scopolamine induced amnesia by almond. Copyright © 2015 Elsevier Inc. All rights reserved.

Noninvasive ergonovine maleate provocative testing for coronary artery spasm: the need for routine thallium-201 imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shanes, J.G.; Krone, R.J.; Fisher, K.

1983-01-01

We administered ergonovine and used both electrocardiographic monitoring and thallium-/sup 201/ (/sup 201/Tl) imaging to detect reversible ischemia in 100 patients. Patients already established as having coronary artery spasm and those with nonbypassed, proximal, high-grade coronary artery stenosis were excluded. No complication occurred in any patient. The use of thallium imaging in addition to electrocardiographic monitoring resulted in a higher degree of sensitivity than did ECG monitoring alone. Fourteen patients demonstrated evidence of coronary artery spasm as documented by /sup 201/Tl imaging but of the 14, significant ECG changes occurred in only 50%, and classic ST segment elevation in 21%.more » Thus, in carefully selected patients the noninvasive provocation of coronary spasm can be accomplished safely, but ECG monitoring must be combined with thallium-/sup 201/ imaging to achieve an acceptable degree of sensitivity.« less

Aggregated data from two double-blind base station provocation studies comparing individuals with idiopathic environmental intolerance with attribution to electromagnetic fields and controls.

PubMed

Eltiti, Stacy; Wallace, Denise; Russo, Riccardo; Fox, Elaine

2015-02-01

Data from two previous studies were aggregated to provide a statistically powerful test of whether exposure to electromagnetic fields (EMFs) produced by telecommunication base stations negatively affects well-being in individuals who report idiopathic environmental illness with attribution to electromagnetic fields (IEI-EMF) and control participants. A total of 102 IEI-EMF and 237 controls participated in open provocation trials and 88 IEI-EMF and 231 controls went on to complete double-blind trials in which they were exposed to EMFs from a base station emitting either a Global System for Mobile Communication and Universal Mobile Telecommunications System or a Terrestrial Trunked Radio Telecommunications System signal. Both experiments included a comparison sham condition. Visual analog and symptom scales measured subjective well-being. Results showed that IEI-EMF participants reported lower levels of well-being during real compared to sham exposure during open provocation, but not during double-blind trials. Additionally, participants reported lower levels of well-being during high compared to low load trials and this did not interact with radiofrequency-EMF exposure. These findings are consistent with a growing body of literature indicating there is no causal relationship between short-term exposure to EMFs and subjective well-being in members of the public whether or not they report perceived sensitivity to EMFs. © 2015 Wiley Periodicals, Inc.

Aqueous Fraction of Beta vulgaris Ameliorates Hyperglycemia in Diabetic Mice due to Enhanced Glucose Stimulated Insulin Secretion, Mediated by Acetylcholine and GLP-1, and Elevated Glucose Uptake via Increased Membrane Bound GLUT4 Transporters

PubMed Central

Kabir, Ashraf Ul; Samad, Mehdi Bin; Ahmed, Arif; Jahan, Mohammad Rajib; Akhter, Farjana; Tasnim, Jinat; Hasan, S. M. Nageeb; Sayfe, Sania Sarker; Hannan, J. M. A.

2015-01-01

Background The study was designed to investigate the probable mechanisms of anti-hyperglycemic activity of B. Vulgaris. Methodology/Principal Findings Aqueous fraction of B. Vulgaris extract was the only active fraction (50mg/kg). Plasma insulin level was found to be the highest at 30 mins after B. Vulgaris administration at a dose of 200mg/kg. B. Vulgaris treated mice were also assayed for plasma Acetylcholine, Glucagon Like Peptide-1 (GLP-1), Gastric Inhibitory Peptide (GIP), Vasoactive Intestinal Peptide, Pituitary Adenylate Cyclase-Activating Peptide (PACAP), Insulin Like Growth Factor-1 (IGF-1), Pancreatic Polypeptides (PP), and Somatostatin, along with the corresponding insulin levels. Plasma Acetylcholine and GLP-1 significantly increased in B. Vulgaris treated animals and were further studied. Pharmacological enhancers, inhibitors, and antagonists of Acetylcholine and GLP-1 were also administered to the test animals, and corresponding insulin levels were measured. These studies confirmed the role of acetylcholine and GLP-1 in enhanced insulin secretion (p<0.05). Principal signaling molecules were quantified in isolated mice islets for the respective pathways to elucidate their activities. Elevated concentrations of Acetylcholine and GLP-1 in B. Vulgaris treated mice were found to be sufficient to activate the respective pathways for insulin secretion (p<0.05). The amount of membrane bound GLUT1 and GLUT4 transporters were quantified and the subsequent glucose uptake and glycogen synthesis were assayed. We showed that levels of membrane bound GLUT4 transporters, glucose-6-phosphate in skeletal myocytes, activity of glycogen synthase, and level of glycogen deposited in the skeletal muscles all increased (p<0.05). Conclusion Findings of the present study clearly prove the role of Acetylcholine and GLP-1 in the Insulin secreting activity of B. Vulgaris. Increased glucose uptake in the skeletal muscles and subsequent glycogen synthesis may also play a part in the anti-hyperglycemic activity of B. Vulgaris. PMID:25647228

In vivo diagnosis of allergic diseases--allergen provocation tests.

PubMed

Agache, I; Bilò, M; Braunstahl, G-J; Delgado, L; Demoly, P; Eigenmann, P; Gevaert, P; Gomes, E; Hellings, P; Horak, F; Muraro, A; Werfel, T; Jutel, M

2015-04-01

The allergen challenge test has been the mainstay of diagnosis of allergic diseases for a long time since it offers a direct proof of the clinical relevance of a particular allergen for the allergic disease symptoms and severity. Standardisation and availability for daily practice (including safety issues) are still to be refined but most of the challenge tests have safely crossed the border from research tools to diagnostic tests available for daily practice for a well trained clinical staff. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of shoulder internal rotation test with the elbow flexion test in the diagnosis of cubital tunnel syndrome.

PubMed

Ochi, Kensuke; Horiuchi, Yukio; Tanabe, Aya; Morita, Kozo; Takeda, Kentaro; Ninomiya, Ken

2011-05-01

To compare the shoulder internal rotation test-a new, provocative test-with the elbow flexion test in the diagnosis of cubital tunnel syndrome (CubTS). Twenty-five patients with CubTS were examined before and after surgery with 10 seconds each of the elbow flexion and shoulder internal rotation tests. Fifty-four asymptomatic individuals and 14 neuropathy patients with a diagnosis other than CubTS were also examined as control cases. For the shoulder internal rotation test, the patient's upper extremity was kept at 90° abduction, maximum internal rotation, and 10° flexion at the shoulder, with 90° elbow flexion and neutral position of the forearm and wrist, with finger extension. Test results were considered positive if any slight symptom attributable to CubTS occurred within 10 seconds. Extraneural pressure inside the cubital tunnel was intraoperatively measured with the positions of both the elbow flexion and shoulder internal rotation tests, in 15 of the CubTS cases. Statistical analyses were performed using Student's t-test with a confidence level of 95%. The preoperative sensitivity in CubTS cases was 80% in the 10-second shoulder internal rotation test and 36% in the 10-second elbow flexion test, and these differences were significant. None of the control cases had positive results in either test. All the CubTS cases improved with surgery; after surgery, neither test provoked symptoms in any surgical patient. The extraneural pressure increased in both provocative positions with no significant difference. Positive results for the 10-second shoulder internal rotation test were more sensitive than that for the elbow flexion test of the same duration and seemed specific to CubTS. Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

ALLERGEN PROVOCATION AUGMENTS ENDOTOXIN-INDUCED NASAL INFLAMMATION IN ATOPIC ASTHMATICS

EPA Science Inventory

Background: Recent epidemiologic and in vivo studies have suggested that inhaled endotoxin plays an important role in asthma pathogenesis.
Objective: The present study examines the effect of nasal allergen provocation on subsequent endotoxin challenges in subjects with atopi...

Alcohol's effect on triggered displaced aggression.

PubMed

Aviles, Fredy; Earleywine, Mitchell; Pollock, Vicki; Stratton, Joy; Miller, Norman

2005-03-01

The authors examined alcohol's effect on triggered displaced aggression, the hostile reaction to a second provoking person after provocation from a first. Participants consumed an alcoholic or a nonalcoholic beverage. Subsequently, one individual provoked all of them with moderate intensity. Then, 2 groups were studied: those who received or who failed to receive a second provocation of minimal intensity. Consistent with prior research, participants who received a second, minimal provocation displayed more aggression than those who did not. After participants drank alcohol, the magnitude of this difference was significantly greater, indicating that alcohol increases triggered displaced aggression. Copyright (c) 2005 APA, all rights reserved.

Social provocation modulates decision making and feedback processing: Examining the trajectory of development in adolescent participants.

PubMed

Pincham, Hannah L; Wu, Claire; Killikelly, Clare; Vuillier, Laura; Fearon, R M Pasco

2015-10-01

Increasingly, research is turning to the ways in which social context impacts decision making and feedback processing in adolescents. The current study recorded electroencephalography to examine the trajectory of development across adolescence, with a focus on how social context impacts cognition and behaviour. To that end, younger (10-12 years) and older (14-16 years) adolescents played a modified Taylor Aggression Paradigm against two virtual opponents: a low-provoker and a high-provoker. During the task's decision phase (where participants select punishment for their opponent), we examined two event-related potentials: the N2 and the late positive potential (LPP). During the outcome phase (where participants experience win or loss feedback), we measured the feedback related negativity (FRN). Although N2 amplitudes did not vary with provocation, LPP amplitudes were enhanced under high provocation for the younger group, suggesting that emotional reactivity during the decision phase was heightened for early adolescents. During the outcome phase, the FRN was reduced following win outcomes under high provocation for both groups, suggesting that a highly provocative social opponent may influence the reward response. Collectively, the data argue that social context is an important factor modulating neural responses in adolescent behavioural and brain development. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Shoulder internal rotation elbow flexion test for diagnosing cubital tunnel syndrome.

PubMed

Ochi, Kensuke; Horiuchi, Yukio; Tanabe, Aya; Waseda, Makoto; Kaneko, Yasuhito; Koyanagi, Takahiro

2012-06-01

Shoulder internal rotation enhances symptom provocation attributed to cubital tunnel syndrome. We present a modified elbow flexion test--the shoulder internal rotation elbow flexion test--for diagnosing cubital tunnel syndrome. Fifty-five ulnar nerves in cubital tunnel syndrome patients and 123 ulnar nerves in controls were examined with 5 seconds each of elbow flexion, shoulder internal rotation, and shoulder internal rotation elbow flexion tests before and after treatment (surgery in 18; conservative in others). For the shoulder internal rotation elbow flexion test position, 90° abduction, maximum internal rotation, and 10° flexion of the shoulder were combined with the elbow flexion test position. The test was considered positive if any symptom for cubital tunnel syndrome developed <5 seconds. Influence of the shoulder internal rotation elbow flexion test was evaluated by nerve conduction studies in 10 cubital tunnel syndrome nerves and 7 control nerves. The sensitivities/specificities of the 5-second elbow flexion, shoulder internal rotation, and shoulder internal rotation elbow flexion tests were 25%/100%, 58%/100%, and 87%/98%, respectively. Sensitivity differences between the shoulder internal rotation elbow flexion test and the other two tests were significant. Shoulder internal rotation elbow flexion test results and cubital tunnel syndrome symptoms were significantly correlated. Influence of the shoulder internal rotation elbow flexion test on the ulnar nerve was seen in 8 of 10 cubital tunnel syndrome nerves but not in controls. The 5-second shoulder internal rotation elbow flexion test is specific, easy and quick provocative test for diagnosing cubital tunnel syndrome. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Clothing and Attributions Concerning Sexual Harassment.

ERIC Educational Resources Information Center

Johnson, Kim K. P.; Workman, Jane E.

1992-01-01

Photographs shown to 98 male and 102 female students illustrated provocative versus nonprovocative clothing on both men and women. Subjects rated provocative clothing more likely to induce sexual harassment. Females who had not experienced harassment rated those wearing nonprovocative clothing unlikely to be harassed. (SK)

Inspiring Reading Success: Interest and Motivation in an Age of High-Stakes Testing

ERIC Educational Resources Information Center

Fink, Rosalee, Ed.; Samuels, S. Jay, Ed.

2007-01-01

Although recent U.S. legislation has had a profound impact on reading instruction and student achievement, some students continue to fall behind. This provocative text addresses this gap with a new perspective on reading instruction that goes beyond the realms of teacher content knowledge and methodology. The book shows how motivation and interest…

Centralization as a predictor of provocation discography results in chronic low back pain, and the influence of disability and distress on diagnostic power.

PubMed

Laslett, Mark; Oberg, Birgitta; Aprill, Charles N; McDonald, Barry

2005-01-01

The "centralization phenomenon" (CP) is the progressive retreat of referred pain towards the spinal midline in response to repeated movement testing (a McKenzie evaluation). A previous study suggested that it may have utility in the clinical diagnosis of discogenic pain and may assist patient selection for discography and specific treatments for disc pain. Estimation of the diagnostic predictive power of centralization and the influence of disability and patient distress on diagnostic performance, using provocation discography as a criterion standard for diagnosis, in chronic low back pain patients. This study was a prospective, blinded, concurrent, reference standard-related validity design carried out in a private radiology clinic specializing in diagnosis of chronic spinal pain. Consecutive patients with persistent low back pain were referred to the study clinic by orthopedists and other medical specialists for interventional radiological diagnostic procedures. Patients were typically disabled and displayed high levels of psychosocial distress. The sample included patients with previous lumbar surgery, and most had unsuccessful conservative therapies previously. results of provocation discography. The CP. Psychometric evaluation: Roland-Morris, Zung, Modified Somatic Perception questionnaires, Distress Risk Assessment Method, and 100-mm visual analog scales for pain intensity. Patients received a single physical therapy examination, followed by lumbar provocation discography. Sensitivity, specificity, and likelihood ratios of the CP were estimated in the group as a whole and in subgroups defined by psychometric measures. A total of 107 patients received the clinical examination and discography at two or more levels and post-discography computed tomography. Thirty-eight could not tolerate a full physical examination and were excluded from the main analysis. Disability and pain intensity ratings were high, and distress was common. Sensitivity, specificity, and positive likelihood ratios for centralization observed during repeated movement testing for pain distribution and intensity changes were 40%, 94%, and 6.9 respectively. In the presence of severe disability, sensitivity, specificity, and positive likelihood ratios were 46%, 80%, 3.2 and for distress, 45%, 89%, 4.1. In the subgroups with moderate, minimal, or no disability, sensitivity and specificity were 37%, 100% and for no or minimal distress 35%, 100%. Centralization is highly specific to positive discography but specificity is reduced in the presence of severe disability or psychosocial distress.

Rhinoconjunctivitis and asthma caused by vine pollen: a case report.

PubMed

Feo Brito, F; Martínez, A; Palacios, R; Mur, P; Gómez, E; Galindo, P A; Borja, J; Martínez, J

1999-02-01

The vine (Vitis vinifera) is a cultivated plant that is found in some European and American countries. Its pollen gathers in small quantities during a short pollination period in the months of May and June. Allergy to vine pollen has not been previously documented. We sought to describe a case report of allergy to vine pollen documented on the basis of anamnesis, cutaneous, provocation, and specific IgE determination tests. An allergenic extract was obtained from collected V vinifera pollens by aqueous standard procedures. Pollen counts and pollination periods of this and other common pollens in the area where the patient became symptomatic were studied. Cutaneous tests and the presence of specific IgE to the pollen extracts were performed by prick, CAP, and RAST techniques. Bronchial and conjunctival tests with the involved pollen extracts were also carried out to identify the sensitizing allergens. Five healthy subjects and 5 pollinic patients were used as control subjects and underwent the same tests. Skin prick test responses with vine pollen at different concentrations were positive for the studied patient and negative for the control subjects. Patient serum revealed a total IgE titer of 334 IU/mL and a specific IgE value of 1.3 PRU/mL (RAST class 2) to vine pollen. Bronchial and conjunctival provocation test responses were also positive when the patient was challenged with V vinifera extract. Exposure to the pollen of the vineyard plants (V vinifera) can induce immunologic sensitization and rhinoconjunctivitis/asthma.

Methacholine challenge testing: improved patient comfort with a 2-tiered protocol.

PubMed

Segel, Michael J; Rabinovich, Einat; Schwarz, Yehuda; Ben-Dov, Issahar

2013-06-01

The methacholine challenge test (MCT) is a test of bronchial hyperreactivity used as an aid in the diagnosis of asthma. MCT results are reported as the provocation concentration at which the forced expiratory volume in 1 second (FEV1) decreases 20% (PC20). The requirement for a 20% or greater decrease in FEV1 results in precipitous decreases in FEV1 in some patients. To improve MCT safety without compromising accuracy. We performed a retrospective analysis of 879 consecutive MCTs (derivation cohort). A novel protocol for MCT was developed and validated in a cohort of 564 MCTs performed in a second institution. In comparison with a PC20 cutoff of less than 8 mg/mL, a provocation concentration at which the FEV1 decreases 10% (PC10) cutoff of 1 mg/mL or less has a sensitivity of 86%, a specificity of 98%, a positive predictive value (PPV) of 97%, and a negative predictive value (NPV) of 91%. We propose a novel 2-tiered protocol for MCT. If the PC10 is 1 mg/mL or less, bronchial hyperreactivity is present; if the PC10 is greater than 1 mg/mL, the test is continued until the provocative concentration is 8 mg/mL or a 20% decrease in FEV1 is achieved. Compared with the standard protocol, the proposed protocol has a sensitivity, specificity, PPV, NPV, and overall accuracy of 100%, 98%, 97.6%, 100%, and 99%, respectively. The modified protocol would have enabled us to avoid 26 of 42 cases (62%) in which a 40% or greater decrease in FEV1 occurred and would save 0.65 dose for every MCT performed. The 2-tiered protocol performed well in the validation cohort; sensitivity, specificity, PPV, NPV, and overall accuracy were 100%, 98%, 87%, 100%, and 98%, respectively. The proposed 2-tiered protocol is accurate, saves time, and avoids precipitous decreases in FEV1. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Asthma-like symptoms, atopy, and bronchial responsiveness in furniture workers.

PubMed

Talini, D; Monteverdi, A; Benvenuti, A; Petrozzino, M; Di Pede, F; Lemmi, M; Carletti, A; Macchioni, P; Serretti, N; Viegi, G; Paggiaro, P

1998-11-01

To study the role of individual and occupational risk factors for asthma in furniture workers. 296 workers were examined (258 men, 38 women) with a questionnaire of respiratory symptoms and diseases, baseline spirometry, bronchial provocative test with methacholine, and skin prick tests. Non-specific bronchial hyperreactivity was defined as when a provocative dose with a fall of 20% in forced expiratory volume in 1 second (PD20FEV1) was < 0.8 mg and atopy in the presence of at least one positive response to skin prick tests. Workers were subdivided into spray painters (exposed to low concentrations of diisocyanates and solvents), woodworkers (exposed to wood dusts), and assemblers (control group). The prevalences of attacks of shortness of breath with wheezing and dyspnoea were higher in spray painters (13.5% and 11.5% respectively) than in woodworkers (7.7% and 6.3%) or in assemblers (1.6% and 1.6%); prevalences of chronic cough, asthma, and rhinitis were also slightly but not significantly higher in spray painters and in woodworkers than in assemblers. The difference in the prevalence of respiratory symptoms among the job titles was due to the atopic subjects, who showed a higher prevalence of chronic cough, wheeze, shortness of breath with wheeze, dyspnoea, and asthma in spray painters than in the other groups. The prevalence of non-specific bronchial hyperreactivity in subjects who performed bronchial provocative tests was 17.7%, with no significant difference among groups. Asthma symptoms were significantly associated with non-specific bronchial hyperreactivity. Asthma-like symptoms plus non-specific bronchial hyperreactivity was found in 4% of assemblers, 10% of woodworkers, and 13.3% of spray painters (chi 2 = 2.6, NS). Multiple logistic analysis taking into account individual (smoke, atopy, age) and occupational (job titles) risk factors confirmed that spray painters had higher prevalence of chronic cough than assemblers, and a trend in increasing the prevalence of shortness of breath with wheeze, dyspnoea, and asthma. Painters in the furniture industry, particularly atopic subjects, are at higher risk of asthma-like symptoms than other job titles. In these workers asthma-like symptoms are more sensitive than non-specific bronchial hyperreactivity in detecting a negative effect of the occupational exposure.

A novel gel based vehicle for the delivery of acetylcholine in quantitative sudomotor axon reflex testing.

PubMed

Sletten, David M; Kimpinski, Kurt; Weigand, Stephen D; Low, Phillip A

2009-10-05

This study describes a novel gel based vehicle for the delivery of acetylcholine (ACh) during quantitative sudomotor axon reflex testing (QSART). A dose and current response study were undertaken on 20 healthy control participants to characterize the efficiency of a gel based vehicle for the delivery of ACh. Values obtained for total sweat volume and latency to sweat onset with gel iontophoresis of ACh during QSART were comparable to previously published normative data using solution based vehicles. Patient discomfort, utilizing the gel based vehicle during the QSART procedure, was minimal. Improvement in iontophoresis using the gel formulation as a vehicle for ACh delivery has the potential to lower the voltage required to overcome skin resistance during QSART and may result in improved patient comfort during the procedure.

Histaminergic and cholinergic neuron systems in the impairment of human thermoregulation during motion sickness.

PubMed

Nobel, Gerard; Tribukait, Arne; Mekjavic, Igor B; Eiken, Ola

2010-05-31

Motion sickness (MS) exaggerates body cooling during cold-water immersion. The aim of the present study was to investigate whether such MS-induced predisposition to hypothermia is influenced by two anti-MS drugs: the histamine-receptor blocker dimenhydrinate (DMH) and the muscarine-receptor blocker scopolamine (Scop). Nine healthy male subjects were immersed in 15 degrees C water for a maximum of 90min in five conditions: (1) control (CN): no medication, no MS provocation; (2) MS-control (MS-CN): no medication, MS provocation; (3) MS-placebo (MS-P): placebo DMH and placebo Scop, MS provocation; (4) MS-DMH: DMH and placebo Scop, MS provocation; (5) MS-Scop: Scop and placebo DMH, MS provocation. MS was induced by use of a rotating chair. Throughout the experiments rectal temperature (T(re)), the difference in temperature between the non-immersed right forearm and third finger (T(ff)) as an index of peripheral vasoconstriction, and oxygen uptake (VO(2)) as a measure of shivering thermogenesis, were recorded. DMH and Scop were similarly efficacious in ameliorating nausea. The fall in T(re) was greater in the MS-CN and MS-P conditions than in the CN condition. DMH, but not Scop, prevented the MS-induced increase in body-core cooling. MS attenuated the cold-induced vasoconstriction, an effect which was fully prevented by DMH but only partially by Scop. MS provocation did not affect VO(2) in any condition. The results suggest that the MS-induced predisposition to hypothermia is predominantly mediated by histaminergic mechanisms and that DMH might be useful in conjunction with maritime accidents or other scenarios where exposure to cold and MS are imminent features. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Species differences in the negative inotropic effect of acetylcholine and soman in rat, guinea pig, and rabbit hearts. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maxwell, D.M.; Thomsen, R.H.; Baskin, S.I.

1991-12-31

Acetylcholine reduced atrial contractions by 82.5% in guinea pig, 50.8% in rat, and 41.5% in rabbit. 2. The EC50, values for the negative inotropic effect of acetylcholine were 3.3 x 10(-7) M in rat and guinea pig atria and 4.1 x 10(-6) M in rabbit atria. 3. There was no correlation between the species differences in the negative inotropic effect of acetylcholine in atria and the density or affinity of acetylcholinesterase or muscarinic receptors. 4. Inhibition of atrial acetylcholinesterase with soman reduced the EC50 of acetylcholine three-fold in all species, but did not change the maximal inotropic effect of acetylcholine.more » 5. Species differences in the negative inotropic effect of acetylcholine may be caused by differences in the coupling between myocardial muscarinic receptors and the ion channels that mediate negative inotropy. Acetylcholine, cardiovascular response, species variation negative inotropic response.« less

Functional Expression of Two Neuronal Nicotinic Acetylcholine Receptors from cDNA Clones Identifies a Gene Family

NASA Astrophysics Data System (ADS)

Boulter, Jim; Connolly, John; Deneris, Evan; Goldman, Dan; Heinemann, Steven; Patrick, Jim

1987-11-01

A family of genes coding for proteins homologous to the α subunit of the muscle nicotinic acetylcholine receptor has been identified in the rat genome. These genes are transcribed in the central and peripheral nervous systems in areas known to contain functional nicotinic receptors. In this paper, we demonstrate that three of these genes, which we call alpha3, alpha4, and beta2, encode proteins that form functional nicotinic acetylcholine receptors when expressed in Xenopus oocytes. Oocytes expressing either alpha3 or alpha4 protein in combination with the beta2 protein produced a strong response to acetylcholine. Oocytes expressing only the alpha4 protein gave a weak response to acetylcholine. These receptors are activated by acetylcholine and nicotine and are blocked by Bungarus toxin 3.1. They are not blocked by α -bungarotoxin, which blocks the muscle nicotinic acetylcholine receptor. Thus, the receptors formed by the alpha3, alpha4, and beta2 subunits are pharmacologically similar to the ganglionic-type neuronal nicotinic acetylcholine receptor. These results indicate that the alpha3, alpha4, and beta2 genes encode functional nicotinic acetylcholine receptor subunits that are expressed in the brain and peripheral nervous system.

The site of the 5-hydroxytryptamine receptor on the intramural nervous plexus of the guinea-pig isolated ileum

PubMed Central

Brownlee, G.; Johnson, E. S.

1963-01-01

Dose/response measurements were made on the guinea-pig isolated ileum with six agonists, acetylcholine, 5-hydroxytryptamine, nicotine, dimethylphenylpiperazinium, choline phenyl ether and histamine. The dose effects were repeated in the presence of each of twelve antagonists and one anticholinesterase. Acetylcholine and histamine were chosen because of their direct mode of action on smooth muscle, nicotine, dimethylphenylpiperazinium and choline phenyl ether were used as examples of drugs that act at the ganglionic acetylcholine receptor. 5-Hydroxytryptamine was the drug investigated. Hyoscine blocked the contractions caused by acetylcholine, 5-hydroxytryptamine and the ganglion-stimulants but left the responses to histamine unchanged. The anticholinesterase N,N'-diisopropylphosphorodiamidic fluoride (mipafox) potentiated all the agonists except histamine. The strength of potentiation decreased in the order 5-hydroxytryptamine, nicotine, dimethylphenylpiperazinium and choline phenyl ether, and acetylcholine. The local anaesthetic procaine inhibited to the same extent contractions elicited by 5-hydroxytryptamine, nicotine, dimethylphenylpiperazinium and choline phenyl ether. These results showed that 5-hydroxytryptamine, like nicotine, choline phenyl ether and dimethylphenylpiperazinium, mediated its response through the nervous plexus. Of those tested 5-hydroxytryptamine was the only specific antagonist to 5-hydroxytryptamine; lysergic acid derivatives produced spasm and prolonged changes in tone; phenoxybenzamine caused non-specific block. The diverse modes of action of a number of ganglion-blocking agents were selectively used. Thus hexamethonium, pentolinium, and nicotine in its competitive phase, blocked contractions due to nicotine, dimethylphenylpiperazinium and choline phenyl ether and left those due to 5-hydroxytryptamine, acetylcholine and histamine unchanged. The depolarizing ganglion-blocking agents, dimethylphenylpiperazinium and nicotine, inhibited the responses to all the indirectly acting drugs. Furthermore, mecamylamine, a drug with a less well-defined mode of action, partially inhibited contractions due to 5-hydroxytryptamine in a concentration that blocked those due to nicotine, dimethylphenylpiperazinium and choline phenyl ether. Pempidine, known to act like mecamylamine, did not antagonize 5-hydroxytryptamine. It is concluded that 5-hydroxytryptamine activates specific receptors sited at the intramural parasympathetic ganglion cells. PMID:14081661

Assessment of vibration produced by the grinders used in the shipbuilding industry of Korea.

PubMed

Park, Hee-Sok; Yim, Sang-Hyuk

2007-04-01

The objective of this study is to estimate the prevalence of finger blanching among the workers in a shipyard of Korea using the dose-response relationship suggested by ISO 5349. The characteristics of vibration exposure produced by six types of grinders were investigated. Vibration measurement was made under the real work conditions. Exposure time was estimated by questionnaire and direct observation. In addition, cold provocation tests were performed, and the results from the tests were compared with the estimated prevalence. As a result, 4 hour-energy-equivalent frequency-weighted accelerations of the finishing grinding (FG) and the prepainting grinding (PG) jobs were 6.23 m/s(2) and 13.39 m/s(2), respectively. The mean exposure time for holding the grinders was 4.64 h per day. Using the ISO 5349 method, it was predicted that after exposure to vibration for 10.79 yr, about a half of the FG workers could develop finger blanching. For the PG workers, the corresponding predicted latency was 5.02 yr. A discrepancy was found between the results from the ISO relationship and those from the cold provocation tests. A linear regression model was suggested employing vibration acceleration and vibration exposure time as explanatory variables for vascular dysfunction.

Detection of Growth Hormone Deficiency in Adults with Chronic Traumatic Brain Injury

PubMed Central

Griesbach, Grace S.; Ashley, Mark J.

2016-01-01

Abstract This study examined the prevalence of growth hormone deficiency (GHD) in patients with traumatic brain injury (TBI) during the post-acute phase of recovery and whether GHD was associated with increased disability, decreased independence, and depression. A secondary objective was to determine the accuracy of insulin-like growth factor-1 (IGF-1) levels in predicting GHD in patients with TBI. Anterior pituitary function was assessed in 235 adult patients with TBI through evaluation of fasting morning hormone levels. GH levels were assessed through provocative testing, specifically the glucagon stimulation test. GHD was diagnosed in a significant number of patients, with 45% falling into the severe GHD (≤3 μg/L) category. IGF-1 levels were not predictive of GHD. Patients with GHD were more disabled and less independent compared with those patients who were not GHD. Those patients with more severe GHD also showed decreased levels of cortisol and testosterone. Symptoms of depression were also more prevalent in this group. In addition, patients with severe GHD had delayed admission to post-acute rehabilitation. This study confirms the high prevalence of GHD in patients with TBI and the necessity to monitor clinical symptoms and perform provocative testing to definitively diagnose GHD. PMID:26414093

Role of motivation to respond to provocation, the social environment, and trait aggression in alcohol-related aggression.

PubMed

Tremblay, Paul F; Mihic, Ljiljana; Graham, Kathryn; Jelley, Jennifer

2007-01-01

Little attention has been paid to the motivation to respond to provocation and to the interaction between this motivation, alcohol, the drinking environment, and individual characteristics. Undergraduates at six Canadian universities (N = 1,232) read three vignettes describing conflict situations with social environmental manipulations while imagining themselves as either sober or intoxicated. Self-ratings assessed likelihood of assertive and aggressive responses and motivational indices of anger, offensiveness of the instigator's actions, and importance to respond to the provocation. Respondents also completed a measure of trait aggression. Multi-group structural equation models supported the hypothesis that perceived likelihood of reactive aggression is influenced by perceived alcohol intoxication, gender, trait aggression, social environmental factors, and motivation to respond to the provocation. In addition, a number of interactions were found among the predictors. These results provide insight into the types of factors that may influence aggression in drinking situations. Copyright 2007 Wiley-Liss, Inc.

Ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppressing nicotinic acetylcholine receptor-ion channels in cultured bovine adrenal medullary cells.

PubMed

Li, Xiaojia; Toyohira, Yumiko; Horisita, Takafumi; Satoh, Noriaki; Takahashi, Keita; Zhang, Han; Iinuma, Munekazu; Yoshinaga, Yukari; Ueno, Susumu; Tsutsui, Masato; Sata, Takeyoshi; Yanagihara, Nobuyuki

2015-12-01

Ikarisoside A is a natural flavonol glycoside derived from plants of the genus Epimedium, which have been used in Traditional Chinese Medicine as tonics, antirheumatics, and aphrodisiacs. Here, we report the effects of ikarisoside A and three other flavonol glycosides on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. We found that ikarisoside A (1-100 μM), but not icariin, epimedin C, or epimedoside A, concentration-dependently inhibited the secretion of catecholamines induced by acetylcholine, a physiological secretagogue and agonist of nicotinic acetylcholine receptors. Ikarisoside A had little effect on catecholamine secretion induced by veratridine and 56 mM K(+). Ikarisoside A (1-100 μM) also inhibited (22)Na(+) influx and (45)Ca(2+) influx induced by acetylcholine in a concentration-dependent manner similar to that of catecholamine secretion. In Xenopus oocytes expressing α3β4 nicotinic acetylcholine receptors, ikarisoside A (0.1-100 μM) directly inhibited the current evoked by acetylcholine. It also suppressed (14)C-catecholamine synthesis and tyrosine hydroxylase activity induced by acetylcholine at 1-100 μM and 10-100 μM, respectively. The present findings suggest that ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppression of nicotinic acetylcholine receptor-ion channels in bovine adrenal medullary cells.

Diagnostic methods for insect sting allergy.

PubMed

Hamilton, Robert G

2004-08-01

This review overviews advances from mid-2002 to the present in the validation and performance methods used in the diagnosis of Hymenoptera venom-induced immediate-type hypersensitivity. The general diagnostic algorithm for insect sting allergy is initially discussed with an examination of the AAAAI's 2003 revised practice parameter guidelines. Changes as a result of a greater recognition of skin test negative systemic reactors include repeat analysis of all testing and acceptance of serology as a complementary diagnostic test to the skin test. Original data examining concordance of venom-specific IgE results produced by the second-generation Pharmacia CAP System with the Johns Hopkins University radioallergosorbent test are presented. Diagnostic performance of honeybee venom-specific IgE assays used in clinical laboratories in North America is discussed using data from the Diagnostic Allergy Proficiency Survey conducted by the College of American Pathologists. Validity of venom-specific IgE antibody in postmortem blood specimens is demonstrated. The utility of alternative in-vivo (provocation) and in-vitro (basophil-based) diagnostic testing methods is critiqued. This overview supports the following conclusions. Improved practice parameter guidelines include serology and skin test as complementary in supporting a positive clinical history during the diagnostic process. Data are provided which support the analytical performance of commercially available venom-specific IgE antibody serology-based assays. Intentional sting challenge in-vivo provocation, in-vitro basophil flow cytometry (CD63, CD203c) based assays, and in-vitro basophil histamine and sulfidoleukotriene release assays have their utility in the study of difficult diagnostic cases, but their use will remain as supplementary, secondary diagnostic tests.

Cervical radiofrequency neurotomy reduces central hyperexcitability and improves neck movement in individuals with chronic whiplash.

PubMed

Smith, Ashley Dean; Jull, Gwendolen; Schneider, Geoff; Frizzell, Bevan; Hooper, Robert Allen; Sterling, Michele

2014-01-01

This study aims to determine if cervical medial branch radiofrequency neurotomy reduces psychophysical indicators of augmented central pain processing and improves motor function in individuals with chronic whiplash symptoms. Prospective observational study of consecutive patients with healthy control comparison. Tertiary spinal intervention centre in Calgary, Alberta, Canada. Fifty-three individuals with chronic whiplash associated disorder symptoms (Grade 2); 30 healthy controls. Measures were made at four time points: two prior to radiofrequency neurotomy, and 1- and 3-months post-radiofrequency neurotomy. Measures included: comprehensive quantitative sensory testing (including brachial plexus provocation test), nociceptive flexion reflex, and motor function (cervical range of movement, superficial neck flexor activity during the craniocervical flexion test). Self-report pain and disability measures were also collected. One-way repeated measures analysis of variance and Friedman's tests were performed to investigate the effect of time on the earlier measures. Differences between the whiplash and healthy control groups were investigated with two-tailed independent samples t-test or Mann-Whitney tests. Following cervical radiofrequency neurotomy, there were significant early (within 1 month) and sustained (3 months) improvements in pain, disability, local and widespread hyperalgesia to pressure and thermal stimuli, nociceptive flexor reflex threshold, and brachial plexus provocation test responses as well as increased neck range of motion (all P < 0.0001). A nonsignificant trend for reduced muscle activity with the craniocervical flexion test (P > 0.13) was measured. Attenuation of psychophysical measures of augmented central pain processing and improved cervical movement imply that these processes are maintained by peripheral nociceptive input. Wiley Periodicals, Inc.

The 'think test': a further technique to elicit hyperventilation.

PubMed Central

Nixon, P G; Freeman, L J

1988-01-01

Hyperventilation can undermine cardiovascular homeostasis by generating autonomic imbalance, sympathetic dominance, hypokalaemia, and intracellular alkalosis with calcium ion shifts. The role of hyperventilation in episodic disorders such as arrhythmia and coronary vasospasm can be difficult to identify if the patient does not present in an attack and so a provocation challenge is required. Today, the standard challenge is the forced hyperventilation provocation test (FHPT). A capnograph enables the resting end-tidal PCO2 to be compared with the level 3 min after the period of overbreathing. We report the use of a patient-specific challenge. After the FHPT, the subject is invited to close his eyes and think about the circumstances of an attack, feelings and sensations experienced (breathing is not mentioned) or topics that were seen to disturb the rhythm of breathing when the medical history was taken. A fall of end-tidal PCO2 of 10 mmHg or more lasting at least one minute was taken as a positive response. Out of 57 patients with cardiovascular symptoms suggesting a hypocapnic influence, resting hypocapnia (end-tidal PCO2 = 30 mmHg) was present in 3 (5%). Of the remaining 54, the FHPT was positive in 16 (30%) and the 'think test' in 33 (61%). This suggests that patient-specific stimulation has advantages over an unspecific challenge in testing for episodic hypocapnia. PMID:3133476

Agelenopsis aperta venom and FTX, a purified toxin, inhibit acetylcholine release in Torpedo synaptosomes.

PubMed

Moulian, N; Gaudry-Talarmain, Y M

1993-06-01

The presence of P-type calcium channels in synaptosomes prepared from electric organ of Torpedo marmorata was investigated by using the venom of Agelenopsis aperta, a toxin purified from it, FTX, and its synthetic analog. We analysed the action of these agents on acetylcholine release which was continuously followed using a chemiluminescent assay. Agelenopsis aperta venom, FTX and synthetic FTX inhibit acetylcholine release from synaptosomes induced by a presynaptic membrane depolarization with 60 mM KCl. A stronger inhibition of acetylcholine release was observed with the venom than with FTX (70 and 50%, respectively). Another way of triggering acetylcholine release from Torpedo synaptosomes is to insert in the presynaptic membrane a calcium ionophore A23187 which allows the bypass of the natural calcium channels. The venom of Agelenopsis aperta inhibits A23187-evoked acetylcholine release. Purified and synthetic FTX does not possess this property, suggesting that this inhibition of acetylcholine release was due to other toxins of the venom. Another type of pharmacological sensitivity of Torpedo calcium channels was also demonstrated using omega-conotoxin GVIA. At a concentration of 20 microM, this toxin was able to inhibit about 35% of KCl-evoked acetylcholine release. When FTX + omega-conotoxin GVIA were applied together, the inhibitory effect on KCl-evoked acetylcholine release was not significantly increased in comparison with the one observed with FTX alone. In conclusion, we examined the effect of different agents on acetylcholine release from Torpedo marmorata electric organ synaptosomes; acetylcholine release was elicited with KCl depolarization and followed continuously with a chemiluminescent assay.(ABSTRACT TRUNCATED AT 250 WORDS)

389 Allergic Reactions to Local Anesthetics: Detection by Skin Tests and Subcutaneous Provocation. Analysis of 160 Cases

PubMed Central

Arcanjo, Luiz; Gonçalves Tavares, Tania Maria; Delcourt, Nathalia; Baroni, Juliana; Rios, João; Rios, José Luiz

2012-01-01

Background Adverse reactions to local anesthetics (LA) are frequent and often referred to as allergic. Although immune-mediated reactions are rare, it should be investigated for suspected cases. The objective of this study was to determine the frequency of positive skin test to these drugs in patients with a suspected history of allergic reactions and describe the main socio-demographic characteristics of these individuals. Methods Retrospective study of medical records of patients attended at Policlínica Geral do Rio de Janeiro Allergic Clinic, between 2008 and 2011. The parameters evaluated were the test indication and the patient ages and gender. The drug tested was that the patient had a history of suspicion. Patients underwent skin prick and intradermal tests and subcutaneous provocation. Descriptive statistical analysis of the data was performed. Results It was performed 160 tests (125 female). Three of this total was excluded due to inconclusive results. In women, the highest proportion of tests was in the age group from 41 to 60 years (43%), while in males the higher concentration was at a youngest age group: 21 to 40 years (41%). The most common indication (103 cases, 65%) for the tests was a previous suspected anaphylactic reaction by LA. Seven of 157 tests had a positive result (4.4%), 6 of them occurred in women (4.8%). Only one test resulted in a type of anaphylactic reaction response (0.67%). All patients who presented positive response to the test had a history of per-anesthetic reaction that suggested an immune-mediated mechanism. Conclusions In patients with a history of previous reaction to local anesthetics, the skin tests with these drugs have a key role in the prevention of anaphylaxis, and on guidance for adequate anesthetic procedures.

Human Correlates of Provocative Questions in Pancreatic Pathology

PubMed Central

McDonald, Oliver G.; Maitra, Anirban; Hruban, Ralph H.

2012-01-01

Studies of cell lines and of animal models of pancreatic cancer have raised a number of provocative questions about the nature and origins of human pancreatic cancer and have provided several leads into exciting new approaches for the treatment of this deadly cancer. In addition, clinicians with little or no contact with human pathology have challenged the way that pancreatic pathology is practiced, suggesting that “genetic signals” may be more accurate than today’s multi-modal approach to diagnoses. In this review we consider eight provocative issues in pancreas pathology, with an emphasis on “the evidence derived from man.” PMID:23060061

Emotional reactivity to threat modulates activity in mentalizing network during aggression.

PubMed

Beyer, Frederike; Münte, Thomas F; Erdmann, Christian; Krämer, Ulrike M

2014-10-01

Aggression is a common response to provocation, albeit with considerable interindividual differences. In this fMRI study, we investigated emotional reactivity to threat as possible link between provocation and aggression, as well as the neural correlates of this relationship. We hypothesized that emotional reactivity, measured as fear potentiation (FP) of the startle response, would be negatively associated with aggressive behavior and would modulate neural activity during an aggressive interaction. In 30 healthy female participants, FP was measured as the difference between blink amplitudes while watching threatening vs neutral pictures. Participants subsequently engaged in a variant of the Taylor Aggression Paradigm (TAP), while being scanned. During the TAP, participants selected a punishment level for either a highly provoking or a nonprovoking opponent. There was no difference in aggressive behavior between participants high and low in FP. However, we found a negative correlation between FP and the neural provocation effect in several regions of a network previously associated with mentalizing including the medial prefrontal cortex, precuneus and the temporo-parietal junction. Independently of the FP variability, aggressive behavior correlated with the provocation effect on activity in the caudate nucleus. Our results indicate that during a provocative confrontation, high emotional reactivity to threat suppresses recruitment of the mentalizing network. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Free energy, precision and learning: the role of cholinergic neuromodulation

PubMed Central

Moran, Rosalyn J.; Campo, Pablo; Symmonds, Mkael; Stephan, Klaas E.; Dolan, Raymond J.; Friston, Karl J.

2014-01-01

Acetylcholine (ACh) is a neuromodulatory transmitter implicated in perception and learning under uncertainty. This study combined computational simulations and pharmaco-electroencephalography in humans, to test a formulation of perceptual inference based upon the free energy principle. This formulation suggests that acetylcholine enhances the precision of bottom-up synaptic transmission in cortical hierarchies by optimising the gain of supragranular pyramidal cells. Simulations of a mismatch negativity paradigm predicted a rapid trial-by-trial suppression of evoked sensory prediction error (PE) responses that is attenuated by cholinergic neuromodulation. We confirmed this prediction empirically with a placebo-controlled study of cholinesterase inhibition. Furthermore – using dynamic causal modelling – we found that drug-induced differences in PE responses could be explained by gain modulation in supragranular pyramidal cells in primary sensory cortex. This suggests that acetylcholine adaptively enhances sensory precision by boosting bottom-up signalling when stimuli are predictable, enabling the brain to respond optimally under different levels of environmental uncertainty. PMID:23658161

Acetylcholine in adrenergic terminals of the cat iris

PubMed Central

Ehinger, B.; Falck, B.; Persson, H.; Rosengren, A.-M.; Sporrong, B.

1970-01-01

1. Acetylcholine was bio-assayed in the normal cat iris, and also after selective sympathetic or parasympathetic denervation. Sympathetic denervation caused no significant change in the acetylcholine content of the cat iris, whereas selective parasympathetic denervation reduced the acetylcholine content below the level of detectability, which on the average was at about 5% of the acetylcholine content of the normal iris. 2. It is concluded that if adrenergic terminals contain any acetylcholine, it is less than what is detectable with the methods available at present, and most certainly less than 6% of the acetylcholine content of cholinergic neurones. 3. On the basis of these and other recently obtained observations, the hypothesis of Burn & Rand (1965) of a cholinergic link in the adrenergic transmission is discussed. It is proposed that it is more reasonable to suppose an interaction between peripheral adrenergic and cholinergic terminals than to presume a cholinergic mechanism within adrenergic nerve fibres. PMID:5503282

Acetylcholine in adrenergic terminals of the cat iris.

PubMed

Ehinger, B; Falck, B; Persson, H; Rosengren, A M; Sporrong, B

1970-08-01

1. Acetylcholine was bio-assayed in the normal cat iris, and also after selective sympathetic or parasympathetic denervation. Sympathetic denervation caused no significant change in the acetylcholine content of the cat iris, whereas selective parasympathetic denervation reduced the acetylcholine content below the level of detectability, which on the average was at about 5% of the acetylcholine content of the normal iris.2. It is concluded that if adrenergic terminals contain any acetylcholine, it is less than what is detectable with the methods available at present, and most certainly less than 6% of the acetylcholine content of cholinergic neurones.3. On the basis of these and other recently obtained observations, the hypothesis of Burn & Rand (1965) of a cholinergic link in the adrenergic transmission is discussed. It is proposed that it is more reasonable to suppose an interaction between peripheral adrenergic and cholinergic terminals than to presume a cholinergic mechanism within adrenergic nerve fibres.

Acetylcholine affects osteocytic MLO-Y4 cells via acetylcholine receptors.

PubMed

Ma, Yuanyuan; Li, Xianxian; Fu, Jing; Li, Yue; Gao, Li; Yang, Ling; Zhang, Ping; Shen, Jiefei; Wang, Hang

2014-03-25

The identification of the neuronal control of bone remodeling has become one of the many significant recent advances in bone biology. Cholinergic activity has recently been shown to favor bone mass accrual by complex cellular regulatory networks. Here, we identified the gene expression of the muscarinic and nicotinic acetylcholine receptors (m- and nAChRs) in mice tibia tissue and in osteocytic MLO-Y4 cells. Acetylcholine, which is a classical neurotransmitter and an osteo-neuromediator, not only influences the mRNA expression of the AChR subunits but also significantly induces the proliferation and viability of osteocytes. Moreover, acetylcholine treatment caused the reciprocal regulation of RANKL and OPG mRNA expression, which resulted in a significant increase in the mRNA ratio of RANKL:OPG in osteocytes via acetylcholine receptors. The expression of neuropeptide Y and reelin, which are two neurogenic markers, was also modulated by acetylcholine via m- and nAChRs in MLO-Y4 cells. These results indicated that osteocytic acetylcholine receptors might be a new valuable mediator for cell functions and even for bone remodeling. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Synthesis of poly(ester-carbonate) with a pendant acetylcholine analog for promoting neurite growth.

PubMed

Xing, Dongming; Ma, Lie; Gao, Changyou

2014-10-01

The modification of biodegradable polyesters with bioactive molecules has become an important strategy for controlling neuron adhesion and neurite outgrowth in nerve regeneration. In this study we report a biodegradable poly(ester-carbonate) with a pendant acetylcholine analog, which a neurotransmitter for the enhancement of neuron adhesion and outgrowth. The acetylcholine-functionalized poly(ester-carbonate) (Ach-P(LA-ClTMC)) was prepared by copolymerizing l-lactide (LA) and 5-methyl-5-chloroethoxycarbonyl trimethylene carbonate (ClTMC), followed by quaternization with trimethylamine. The acetylcholine analog content could be modulated by changing the molar feeding fraction of ClTMC. The incorporation of the acetylcholine analog improved the hydrophilicity of the films, but the acetylcholine analog content did not significantly influence the surface morphology of the acetylcholine-functionalized films. The results of PC12 cell culture showed that the acetylcholine analog promoted cell viability and neurite outgrowth in a concentration-dependent manner. The longest length of neurite and the percentage of cells bearing neurites were obtained on the Ach-P(LA-ClTMC)-10 film. All the results indicate that the integration of the acetylcholine analog at an appropriate fraction could be an effective strategy for optimizing the existing biodegradable polyesters for nerve regeneration applications. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Acetylcholine and acetylcarnitine transport in peritoneum: Role of the SLC22A4 (OCTN1) transporter.

PubMed

Pochini, Lorena; Scalise, Mariafrancesca; Di Silvestre, Sara; Belviso, Stefania; Pandolfi, Assunta; Arduini, Arduino; Bonomini, Mario; Indiveri, Cesare

2016-04-01

A suitable experimental tool based on proteoliposomes for assaying Organic Cation Transporter Novel member 1 (OCTN1) of peritoneum was pointed out. OCTN1, recently acknowledged as acetylcholine transporter, was immunodetected in rat peritoneum. Transport was assayed following flux of radiolabelled TEA, acetylcholine or acetylcarnitine in proteoliposomes reconstituted with peritoneum extract. OCTN1 mediated, besides TEA, also acetylcholine and a slower acetylcarnitine transport. External sodium inhibited acetylcholine uptake but not its release from proteoliposomes. Differently, sodium did not affect acetylcarnitine uptake. These results suggested that physiologically, acetylcholine should be released while acetylcarnitine was taken up by peritoneum cells. Transport was impaired by OCTN1 inhibitors, butyrobetaine, spermine, and choline. Biotin was also found as acetylcholine transport inhibitor. Anti-OCTN1 antibody specifically inhibited acetylcholine transport confirming the involvement of OCTN1. The transporter was also immunodetected in human mesothelial primary cells. Extract from these cells was reconstituted in proteoliposomes. Transport features very similar to those found with rat peritoneum were observed. Validation of the proteoliposome model for peritoneal transport study was then achieved assaying transport in intact mesothelial cells. TEA, butyrobetaine and Na(+) inhibited acetylcholine transport in intact cells while efflux was Na(+) insensitive. Therefore transport features in intact cells overlapped those found in proteoliposomes. Copyright © 2015 Elsevier B.V. All rights reserved.

Differential effects of subtype-specific nicotinic acetylcholine receptor agonists on early and late hippocampal LTP.

PubMed

Kroker, Katja S; Rast, Georg; Rosenbrock, Holger

2011-12-05

Brain nicotinic acetylcholine receptors are involved in several neuropsychiatric disorders, e.g. Alzheimer's and Parkinson's diseases, Tourette's syndrome, schizophrenia, depression, autism, attention deficit hyperactivity disorder, and anxiety. Currently, approaches selectively targeting the activation of specific nicotinic acetylcholine receptors are in clinical development for treatment of memory impairment of Alzheimer's disease patients. These are α4β2 and α7 nicotinic acetylcholine receptor agonists which are believed to enhance cholinergic and glutamatergic neurotransmission, respectively. In order to gain a better insight into the mechanistic role of these two nicotinic acetylcholine receptors in learning and memory, we investigated the effects of the α4β2 nicotinic acetylcholine receptor agonist TC-1827 and the α7 nicotinic acetylcholine receptor partial agonist SSR180711 on hippocampal long-term potentiation (LTP), a widely accepted cellular experimental model of memory formation. Generally, LTP is distinguished in an early and a late form, the former being protein-synthesis independent and the latter being protein-synthesis dependent. TC-1827 was found to increase early LTP in a bell-shaped dose dependent manner, but did not affect late LTP. In contrast, the α7 nicotinic acetylcholine receptor partial agonist SSR180711 showed enhancing effects on both early and late LTP in a bell-shaped manner. Furthermore, SSR180711 not only increased early LTP, but also transformed it into late LTP, which was not observed with the α4β2 nicotinic acetylcholine receptor agonist. Therefore, based on these findings α7 nicotinic acetylcholine receptor (partial) agonists appear to exhibit stronger efficacy on memory improvement than α4β2 nicotinic acetylcholine receptor agonists. Copyright © 2011 Elsevier B.V. All rights reserved.

Inferior J waves in patients with vasospastic angina might be a risk factor for ventricular fibrillation.

PubMed

Fumimoto, Tomoko; Ueyama, Takeshi; Shimizu, Akihiko; Yoshiga, Yasuhiro; Ono, Makoto; Kato, Takayoshi; Ishiguchi, Hironori; Okamura, Takayuki; Yamada, Jutaro; Yano, Masafumi

2017-09-01

There is little information about the relationship between J waves and the occurrence of ventricular fibrillation (VF) in patients with vasospastic angina (VSA). The present study aimed to assess the incidence of J waves and the occurrence of VF in patients with VSA. The subjects consisted of 62 patients with VSA diagnosed by acetylcholine provocation tests in our institution from 2002 to 2014. We investigated the VF events, prevalence of J waves, and relationship between the VF events and J waves. J waves were observed in 16 patients (26%) and VF events were documented in 11 (18%). The incidence of VF in the patients with J waves was significantly higher than that in those without J waves (38% vs 11%, p=0.026). J waves were observed in the inferior leads in 14 patients, lateral leads in 5, and anterior leads in 3. A univariate analysis indicated that the incidence of VF in the inferior leads of J wave positive patients (46%=6/14) was significantly (p=0.01) higher than that in the inferior leads of J wave negative patients (10%=5/48). The J waves in the anterior and/or lateral leads were not related to the incidence of VF. Notched type and slurred type J waves were not associated with VF. A multivariate analysis revealed that J waves in VSA patients were associated with VF [odds ratio (OR) 6.41, 95% confidence interval (CI) 1.37-29.93, p=0.02] and organic stenosis (OR 6.98, 95% CI 1.39-35.08, p=0.02). Further, J waves in the inferior leads were strongly correlated with VF (OR 11.85, 95% CI 2.05-68.42, p=0.006). The results suggest that the existence of J waves, especially in the inferior leads, might be a risk factor for VF in VSA patients. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Peer Provocation in Physical Education: Experiences of Botswana Adolescents

ERIC Educational Resources Information Center

Shehu, Jimoh

2009-01-01

Critical incidents of peer provocation in physical education were investigated among 675 junior secondary school students in Botswana. Data were generated through a brief, open-ended questionnaire requesting the students to narrate their experiences of bad, hurtful and offensive peer behaviours during physical education classes. Six overlapping…

Bullying by Definition: An Examination of Definitional Components of Bullying

ERIC Educational Resources Information Center

Goldsmid, Susan; Howie, Pauline

2014-01-01

Lack of definitional consensus remains an important unresolved issue within bullying research. This study examined the ability of definitional variables to predict overall level of victimisation (distress, power inequity, and provocation as predictors) and bullying (intention to harm, power inequity, and provocation as predictors) in 246…

78 FR 48216 - Culturally Significant Objects Imported for Exhibition Determinations: “Balthus: Cats and Girls...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-07

... DEPARTMENT OF STATE [Public Notice 8410] Culturally Significant Objects Imported for Exhibition Determinations: ``Balthus: Cats and Girls--Paintings and Provocations'' SUMMARY: Notice is hereby given of the... that the objects to be included in the exhibition ``Balthus: Cats and Girls--Paintings and Provocations...

Familial Brugada syndrome uncovered by hyperkalaemic diabetic ketoacidosis.

PubMed

Postema, Pieter G; Vlaar, Alexander P J; DeVries, J Hans; Tan, Hanno L

2011-10-01

We describe a case of diabetic ketoacidosis with concomitant hyperkalaemia that uncovered a typical Brugada syndrome electrocardiogram (ECG). Further provocation testing in the patient and his son confirmed familial Brugada syndrome. Diabetic ketoacidosis with hyperkalaemia may uncover an inheritable arrhythmia syndrome that may put the patient and his/her next of kin at risk for a sudden death, irrespective of diabetes mellitus.

Routine Leak Testing in Colorectal Surgery in the Surgical Care and Outcomes Assessment Program

PubMed Central

Kwon, Steve; Morris, Arden; Billingham, Richard; Frankhouse, Joseph; Horvath, Karen; Johnson, Morrie; McNevin, Shane; Simons, Anthony; Symons, Rebecca; Steele, Scott; Thirlby, Richard; Whiteford, Mark; Flum, David R.

2014-01-01

Objective To evaluate the effect of routine anastomotic leak testing (performed to screen for leaks) vs selective testing (performed to evaluate for a suspected leak in a higher-risk or technically difficult anastomosis) on outcomes in colorectal surgery because the value of provocative testing of colorectal anastomoses as a quality improvement metric has yet to be determined. Design Observational, prospectively designed cohort study. Setting Data from Washington state’s Surgical Care and Outcomes Assessment Program (SCOAP). Patients Patients undergoing elective left-sided colon or rectal resections at 40 SCOAP hospitals from October 1, 2005, to December 31, 2009. Interventions Use of leak testing, distinguishing procedures that were performed at hospitals where leak testing was selective (<90% use) or routine (≥90% use) in a given calendar quarter. Main Outcome Measure Adjusted odds ratio of a composite adverse event (CAE) (unplanned postoperative intervention and/or in-hospital death) at routine testing hospitals. Results Among 3449 patients (mean [SD] age, 58.8[14.8] years; 55.0% women), the CAE rate was 5.5%. Provocative leak testing increased (from 56% in the starting quarter to 76% in quarter 16) and overall rates of CAE decreased (from 7.0% in the starting quarter to 4.6% in quarter 16; both P ≤ .01) over time. Among patients at hospitals that performed routine leak testing, we found a reduction of more than 75% in the adjusted risk of CAEs (odds ratio, 0.23; 95% CI, 0.05–0.99). Conclusion Routine leak testing of left-sided colorectal anastomoses appears to be associated with a reduced rate of CAEs within the SCOAP network and meets many of the criteria of a worthwhile quality improvement metric. PMID:22508778

Routine leak testing in colorectal surgery in the Surgical Care and Outcomes Assessment Program.

PubMed

Kwon, Steve; Morris, Arden; Billingham, Richard; Frankhouse, Joseph; Horvath, Karen; Johnson, Morrie; McNevin, Shane; Simons, Anthony; Symons, Rebecca; Steele, Scott; Thirlby, Richard; Whiteford, Mark; Flum, David R

2012-04-01

To evaluate the effect of routine anastomotic leak testing (performed to screen for leaks) vs selective testing (performed to evaluate for a suspected leak in a higher-risk or technically difficult anastomosis) on outcomes in colorectal surgery because the value of provocative testing of colorectal anastomoses as a quality improvement metric has yet to be determined. Observational, prospectively designed cohort study. Data from Washington state's Surgical Care and Outcomes Assessment Program (SCOAP). Patients undergoing elective left-sided colon or rectal resections at 40 SCOAP hospitals from October 1, 2005, to December 31, 2009. Use of leak testing, distinguishing procedures that were performed at hospitals where leak testing was selective (<90% use) or routine (≥ 90% use) in a given calendar quarter. Adjusted odds ratio of a composite adverse event (CAE) (unplanned postoperative intervention and/or in-hospital death) at routine testing hospitals. Among 3449 patients (mean [SD] age, 58.8 [14.8] years; 55.0% women), the CAE rate was 5.5%. Provocative leak testing increased (from 56% in the starting quarter to 76% in quarter 16) and overall rates of CAE decreased (from 7.0% in the starting quarter to 4.6% in quarter 16; both P ≤ .01) over time. Among patients at hospitals that performed routine leak testing, we found a reduction of more than 75% in the adjusted risk of CAEs (odds ratio, 0.23; 95% CI, 0.05-0.99). Routine leak testing of left-sided colorectal anastomoses appears to be associated with a reduced rate of CAEs within the SCOAP network and meets many of the criteria of a worthwhile quality improvement metric.

A study to derive a clinical decision rule for triage of emergency department patients with chest pain: design and methodology

PubMed Central

Hess, Erik P; Wells, George A; Jaffe, Allan; Stiell, Ian G

2008-01-01

Background Chest pain is the second most common chief complaint in North American emergency departments. Data from the U.S. suggest that 2.1% of patients with acute myocardial infarction and 2.3% of patients with unstable angina are misdiagnosed, with slightly higher rates reported in a recent Canadian study (4.6% and 6.4%, respectively). Information obtained from the history, 12-lead ECG, and a single set of cardiac enzymes is unable to identify patients who are safe for early discharge with sufficient sensitivity. The 2007 ACC/AHA guidelines for UA/NSTEMI do not identify patients at low risk for adverse cardiac events who can be safely discharged without provocative testing. As a result large numbers of low risk patients are triaged to chest pain observation units and undergo provocative testing, at significant cost to the healthcare system. Clinical decision rules use clinical findings (history, physical exam, test results) to suggest a diagnostic or therapeutic course of action. Currently no methodologically robust clinical decision rule identifies patients safe for early discharge. Methods/design The goal of this study is to derive a clinical decision rule which will allow emergency physicians to accurately identify patients with chest pain who are safe for early discharge. The study will utilize a prospective cohort design. Standardized clinical variables will be collected on all patients at least 25 years of age complaining of chest pain prior to provocative testing. Variables strongly associated with the composite outcome acute myocardial infarction, revascularization, or death will be further analyzed with multivariable analysis to derive the clinical rule. Specific aims are to: i) apply standardized clinical assessments to patients with chest pain, incorporating results of early cardiac testing; ii) determine the inter-observer reliability of the clinical information; iii) determine the statistical association between the clinical findings and the composite outcome; and iv) use multivariable analysis to derive a highly sensitive clinical decision rule to guide triage decisions. Discussion The study will derive a highly sensitive clinical decision rule to identify low risk patients safe for early discharge. This will improve patient care, lower healthcare costs, and enhance flow in our busy and overcrowded emergency departments. PMID:18254973

Tolerance Following Organophosphate Poisoning of Tracheal Muscle

DTIC Science & Technology

1984-12-13

and the agonists pilocarpine, carbachol and acetylcholine. In order to eliminate hydrolysis of acetylcholine, due to the presence of pseudo- and...tubocurare also inhibited [ H]QNB binding at micromolar concentrations. The cholinergic agonists such as acetylcholine, carbachol and pilocarpine...will be measuring dose-response relationships for acetylcholine, carbachol and histamine in control and tolerant animals. m Electrophysiology: The

D2 dopamine receptor activation inhibits basal and forskolin-evoked acetylcholine release from dissociated striatal cholinergic interneurons.

PubMed

Login, I S

1997-02-21

We tested whether D2 ligands inhibit basal and forskolin-stimulated [3H]ACh release from dissociated striata, as opposed to striatal slices. Quinpirole inhibited both basal (40% maximal inhibition; IC50 approximately 50 nM) and 10 microM forskolin-stimulated release (80% inhibition; IC50 approximately 25 nM quinpirole) and both actions were blocked by a D2 antagonist. Vesamicol prevented the quinpirole and forskolin actions. The ability of D2 agonists to inhibit basal and cyclase-stimulated acetylcholine release emanating from vesamicol-sensitive vesicles appears to be tonically suppressed by inhibitory elements within striatal circuitry.

Prolonged administration of pyridostigmine impairs neuromuscular function with and without down-regulation of acetylcholine receptors.

PubMed

Richtsfeld, Martina; Yasuhara, Shingo; Fink, Heidrun; Blobner, Manfred; Martyn, J A Jeevendra

2013-08-01

The acetylcholinesterase inhibitor, pyridostigmine, is prophylactically administered to mitigate the toxic effects of nerve gas poisoning. The authors tested the hypothesis that prolonged pyridostigmine administration can lead to neuromuscular dysfunction and even down-regulation of acetylcholine receptors. Pyridostigmine (5 or 25 mg·kg·day) or saline was continuously administered via osmotic pumps to rats, and infused for either 14 or 28 days until the day of neuromuscular assessment (at day 14 or 28), or discontinued 24 h before neuromuscular assessment. Neurotransmission and muscle function were examined by single-twitch, train-of-four stimulation and 100-Hz tetanic stimulation. Sensitivity to atracurium and acetylcholine receptor number (quantitated by I-α-bungarotoxin) provided additional measures of neuromuscular integrity. Specific tetanic tensions (Newton [N]/muscle weight [g]) were significantly (P < 0.05) decreased at 14 (10.3 N/g) and 28 (11.1 N/g) days of 25 mg·kg·day pyridostigmine compared with controls (13.1-13.6 N/g). Decreased effective dose (0.81-1.05 vs. 0.16-0.45 mg/kg; P < 0.05) and decreased plasma concentration (3.02-3.27 vs. 0.45-1.37 μg/ml; P < 0.05) of atracurium for 50% paralysis (controls vs. 25 mg·kg·day pyridostigmine, respectively), irrespective of discontinuation of pyridostigmine, confirmed the pyridostigmine-induced altered neurotransmission. Pyridostigmine (25 mg·kg·day) down-regulated acetylcholine receptors at 28 days. Prolonged administration of pyridostigmine (25 mg·kg·day) leads to neuromuscular impairment, which can persist even when pyridostigmine is discontinued 24 h before assessment of neuromuscular function. Pyridostigmine has the potential to down-regulate acetylcholine receptors, but induces neuromuscular dysfunction even in the absence of receptor changes.

Can hip abduction and external rotation discriminate sacroiliac joint pain?

PubMed

Adhia, Divya Bharatkumar; Tumilty, Steve; Mani, Ramakrishnan; Milosavljevic, Stephan; Bussey, Melanie D

2016-02-01

The primary aim of the study is to determine if Hip Abduction and External Rotation (HABER) test is capable of reproducing familiar pain in individuals with low back pain (LBP) of sacroiliac joint (SIJ) origin (SIJ-positive) when compared with LBP of Non-SIJ origin (SIJ-negative). If so, the secondary aim is to determine the diagnostic accuracy of HABER test against the reference standard of pain provocation tests, and to determine which increments of the HABER test has highest sensitivity and specificity for identifying SIJ-positive individuals. Single-blinded diagnostic accuracy study. Participants [n(122)] between ages of 18-50 y, suffering from chronic non-specific LBP (≥3 months) volunteered in the study. An experienced musculoskeletal physiotherapist evaluated and classified participants into either SIJ-positive [n(45)] or SIJ-negative [n(77)], based on reference standard of pain provocation tests [≥3 positive tests = SIJ-positive]. Another musculoskeletal physiotherapist, blinded to clinical groups, evaluated participants for reproduction of familiar pain during each increment (10°, 20°, 30°, 40°, and 50°) of HABER test. The HABER test reproduced familiar pain in SIJ-positive individuals when compared with SIJ-negative individuals [p (0.001), R(2) (0.38), Exp(β) (5.95-10.32)], and demonstrated moderate level of sensitivity (67%-78%) and specificity (71%-72%) for identifying SIJ-positive individuals. Receiver operator curve analysis demonstrated that the HABER increments of ≥30° have the highest sensitivity (83%-100%) and specificity (52%-64%). The HABER test is capable of reproducing familiar pain in SIJ-positive LBP individuals and has moderate levels of sensitivity and specificity for identifying SIJ-positive LBP individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

beta-Phenylethylamine modulates acetylcholine release in the rat striatum: involvement of a dopamine D(2) receptor mechanism.

PubMed

Kato, M; Ishida, K; Chuma, T; Abe, K; Shigenaga, T; Taguchi, K; Miyatake, T

2001-04-20

We examined the effects of beta-phenylethylamine on striatal acetylcholine release in freely moving rats using in vivo microdialysis. beta-Phenylethylamine at 12.5 mg/kg, i.p. did not affect acetylcholine release in the striatum, whereas 25 and 50 mg/kg, i.p. immediately induced an increase in acetylcholine release in the striatum at 15-45 min. This increase following intraperitoneal administration of beta-phenylethylamine (25 mg/kg) was not affected by locally applied SCH-23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine, 10 microM), a dopamine D(1) receptor antagonist, nor by raclopride (10 microM), a dopamine D(2) receptor antagonist. The increased release of acetylcholine induced by beta-phenylethylamine was suppressed by local infusion of tetrodotoxin (1 microM). In contrast, the extracellular acetylcholine level in the striatum was significantly decreased by local application of beta-phenylethylamine (10 and 100 microM) in the striatum via a microdialysis probe. The decrease was completely blocked by local co-application of raclopride (10 microM). The beta-phenylethylamine-induced decrease in striatal acetylcholine release was not affected by co-perfusion with SCH-23390 (10 microM). These results indicate that systemic administration of beta-phenylethylamine increases acetylcholine release, whereas locally applied beta-phenylethylamine decreases striatal acetylcholine release in freely moving rats. Furthermore, the dopaminergic system, through the dopamine D(2) receptor, is involved in the locally applied beta-phenylethylamine-induced decrease in acetylcholine in the striatum.

Acetylcholine Activity in Selective Striatal Regions Supports Behavioral Flexibility

PubMed Central

Ragozzino, Michael E.; Mohler, Eric G.; Prior, Margaret; Palencia, Carlos A.; Rozman, Suzanne

2009-01-01

Daily living often requires individuals to flexibly respond to new circumstances. There is considerable evidence that the striatum is part of a larger neural network that supports flexible adaptations. Cholinergic interneurons are situated to strongly influence striatal output patterns which may enable flexible adaptations. The present experiments investigated whether acetylcholine actions in different striatal regions support behavioral flexibility by measuring acetylcholine efflux during place reversal learning. Acetylcholine efflux selectively increased in the dorsomedial striatum, but not dorsolateral or ventromedial striatum during place reversal learning. In order to modulate the M2-class of autoreceptors, administration of oxotremorine sesquifumurate (100 nM) into the dorsomedial striatum, concomitantly impaired reversal learning and an increase in acetylcholine output. These effects were reversed by the m2 muscarinic receptor antagonist, AF-DX-116 (20 nM). The effects of oxotremorine sesquifumurate and AF-DX-116 on acetylcholine efflux were selective to behaviorally-induced changes as neither treatment affected acetylcholine output in a resting condition. In contrast to reversal learning, acetylcholine efflux in the dorsomedial striatum did not change during place acquisition. The results reveal an essential role for cholinergic activity and define its locus of control to the dorsomedial striatum in cognitive flexibility. PMID:18845266

Acetylcholine activity in selective striatal regions supports behavioral flexibility.

PubMed

Ragozzino, Michael E; Mohler, Eric G; Prior, Margaret; Palencia, Carlos A; Rozman, Suzanne

2009-01-01

Daily living often requires individuals to flexibly respond to new circumstances. There is considerable evidence that the striatum is part of a larger neural network that supports flexible adaptations. Cholinergic interneurons are situated to strongly influence striatal output patterns which may enable flexible adaptations. The present experiments investigated whether acetylcholine actions in different striatal regions support behavioral flexibility by measuring acetylcholine efflux during place reversal learning. Acetylcholine efflux selectively increased in the dorsomedial striatum, but not dorsolateral or ventromedial striatum during place reversal learning. In order to modulate the M2-class of autoreceptors, administration of oxotremorine sesquifumurate (100 nM) into the dorsomedial striatum, concomitantly impaired reversal learning and an increase in acetylcholine output. These effects were reversed by the m(2) muscarinic receptor antagonist, AF-DX-116 (20 nM). The effects of oxotremorine sesquifumurate and AF-DX-116 on acetylcholine efflux were selective to behaviorally-induced changes as neither treatment affected acetylcholine output in a resting condition. In contrast to reversal learning, acetylcholine efflux in the dorsomedial striatum did not change during place acquisition. The results reveal an essential role for cholinergic activity and define its locus of control to the dorsomedial striatum in cognitive flexibility.

Methamphetamine exposure during brain development alters the brain acetylcholine system in adolescent mice

PubMed Central

Siegel, Jessica A.; Park, Byung S.; Raber, Jacob

2013-01-01

Children exposed to methamphetamine during brain development as a result of maternal drug use have long-term hippocampus-dependent cognitive impairments, but the mechanisms underlying these impairments are not understood. The acetylcholine system plays an important role in cognitive function and potential methamphetamine-induced acetylcholine alterations may be related to methamphetamine-induced cognitive impairments. In this study, we investigated the potential long-term effects of methamphetamine exposure during hippocampal development on the acetylcholine system in adolescence mice on postnatal day 30 and in adult mice on postnatal day 90. Methamphetamine exposure increased the density of acetylcholine neurons in regions of the basal forebrain and the area occupied by acetylcholine axons in the hippocampus in adolescent female mice. In contrast, methamphetamine exposure did not affect the density of GABA cells or total neurons in the basal forebrain. Methamphetamine exposure also increased the number of muscarinic acetylcholine receptors in the hippocampus of adolescent male and female mice. Our results demonstrate for the first time that methamphetamine exposure during hippocampal development affects the acetylcholine system in adolescent mice and that these changes are more profound in females than males. PMID:21824143

The Novaco Anger Scale--Provocation Inventory (1994 Version) in Dutch Forensic Psychiatric Patients

ERIC Educational Resources Information Center

Hornsveld, Ruud H. J.; Muris, Peter; Kraaimaat, Floris W.

2011-01-01

We examined the psychometric properties of the Novaco Anger Scale--Provocation Inventory (NAS-PI, 1994 version) in Dutch violent forensic psychiatric patients and secondary vocational students. A confirmatory factor analysis of the subscale structure of the NAS was carried out, reliability was investigated, and relations were calculated between…

Creating Crossroads for Self-Authorship: Investigating the Provocative Moment

ERIC Educational Resources Information Center

Pizzolato, Jane Elizabeth

2005-01-01

Through examination of 613 students' narratives about self-selected important decisions, I investigated the student and situation characteristics related to provocation and use of self authored ways of knowing. The findings gesture toward both particular skills students may need to develop in order to self-author, as well as suggest that movement…

Children's Moral Reasoning about Family and Peer Violence: The Role of Provocation and Retribution.

ERIC Educational Resources Information Center

Astor, Ron A.

1994-01-01

Examined violent and nonviolent inner-city children's moral reasoning about violence in family and peer situations. All of the children condemned unprovoked violence. With provoked situations, the violent group focused more on the immorality of the provocation and perceived force akin to reciprocal justice, whereas the nonviolent group perceived…

Provocative Pedagogies in e-Learning: Making the Invisible Visible

ERIC Educational Resources Information Center

Sinclair, Anne

2009-01-01

The purpose of this case study was to explore the experiences of participants (practicing teachers) involved in an online course entitled: "Reflective Practice for Teachers." Using a provocative pedagogy in the course, the teachers were challenged to confront beliefs and assumptions about teaching and learning and become active participants in the…

Making Choices: Simultaneous Report and Provocative Statements, Tools for Appreciative Inquiry

ERIC Educational Resources Information Center

Nelson, Eric M.; Wright, Christine M.

2011-01-01

Many educators find that students do not participate actively in class, and are constantly seeking a variety of techniques to encourage student participation. The focus of this paper is to show how simultaneous report and provocative statements can be combined to foster appreciative inquiry, thereby, creating a learning environment with greater…

Chemical stimulation of adherent cells by localized application of acetylcholine from a microfluidic system.

PubMed

Zibek, Susanne; Hagmeyer, Britta; Stett, Alfred; Stelzle, Martin

2010-01-01

Chemical stimulation of cells is inherently cell type selective in contrast to electro-stimulation. The availability of a system for localized application of minute amounts of chemical stimulants could be useful for dose related response studies to test new compounds. It could also bring forward the development of a novel type of neuroprostheses. In an experimental setup microdroplets of an acetylcholine solution were ejected from a fluidic microsystem and applied to the bottom of a nanoporous membrane. The solution traveled through the pores to the top of the membrane on which TE671 cells were cultivated. Calcium imaging was used to visualize cellular response with temporal and spatial resolution. Experimental demonstration of chemical stimulation for both threshold gated stimulation as well as accumulated dose-response was achieved by either employing acetylcholine as chemical stimulant or applying calcein uptake, respectively. Numerical modeling and simulation of transport mechanisms involved were employed to gain a theoretical understanding of the influence of pore size, concentration of stimulant and droplet volume on the spatial-temporal distribution of stimulant and on the cellular response. Diffusion, pressure driven flow and evaporation effects were taken into account. Fast stimulation kinetic is achieved with pores of 0.82 μm diameter, whereas sustained substance delivery is obtained with nanoporous membranes. In all cases threshold concentrations ranging from 0.01 to 0.015 μM acetylcholine independent of pore size were determined.

A computational model of the nicotinic acetylcholine binding site

NASA Astrophysics Data System (ADS)

Gálvez-ruano, Enrique; Iriepa-Canalda, Isabel; Morreale, Antonio; Lipkowitz, Kenny B.

1999-01-01

We have derived a model of the nicotinic acetylcholine binding site. This was accomplished by using three known agonists (acetylcholine, nicotine and epibatidine) as templates around which polypeptide side chains, found to be part of the receptor cavity from published molecular biology studies, are allowed to flow freely in molecular dynamics simulations and mold themselves around these templates. The resulting supramolecular complex should thus be a complement, both in terms of steric effects as well as electronic effects, to the agonists and it should be a good estimation of the true receptor cavity structure. The shapes of those minireceptor cavities equilibrated rapidly on the simulation time scale and their structural congruence is very high, implying that a satisfactory model of the nicotinic acetylcholine binding site has been achieved. The computational methodology was internally tested against two rigid and specific antagonists (dihydro-β-erytroidine and erysoidine), that are expected to give rise to a somewhat differently shaped binding site compared to that derived from the agonists. Using these antagonists as templates there were structural reorganizations of the initial receptor cavities leading to distinctly different cavities compared to agonists. This indicates that adequate times and temperatures were used in our computational protocols to achieve equilibrium structures for the agonists. Overall, both minireceptor geometries for agonists and antagonists are similar with the exception of one amino acid (ARG209).

Azithromycin is more allergenic than clarithromycin in children with suspected hypersensitivity reaction to macrolides.

PubMed

Barni, S; Butti, D; Mori, F; Pucci, N; Rossi, M E; Cianferoni, A; Novembre, E

2015-01-01

Macrolides are considered safe antibiotics with reduced allergenic activity. However, studies on the safety of macrolides are scarce, particularly in children. The aim of this study was to assess the frequency of hypersensitivity reactions to clarithromycin and azithromycin in a group of children referred to our allergy unit for suspected macrolide allergy. We retrospectively reviewed the charts of 90 children aged 1-17 years with symptoms suggestive of hypersensitivity reaction to clarithromycin or azithromycin between December 31, 2008 and December 31, 2013. The allergy workup included skin tests (ie, skin prick tests and/or intradermal tests), determination of serum specific IgE (sIgE) to clarithromycin and azithromycin, and, if necessary to reach a diagnosis, oral provocation tests. Seventy-seven children completed the allergy workup. A reaction to clarithromycin was recorded in 58 children (75.3%): 21 (36.2%) had a history of immediate reactions, and 37 (63.8%) had a history of nonimmediate reactions. A reaction to azithromycin was recorded in 19 children (24.6%): 6 (31.5%) had a history of immediate reaction, and 13 (68.42%) had a history of nonimmediate reaction. Positive results in skin tests and oral provocation tests with the suspect drug confirmed the diagnosis in 15.5% of reactions to clarithromycin (9 of 58) and in 47.3% of reactions to azithromycin (9 of 19) (P = .004). A complete allergy workup enabled us to confirm a diagnosis of clarithromycin and azithromycin allergy in 15.5% and 47.3% of cases, respectively. Azithromycin was more allergenic than clarithromycin in children.

Organophosphate acetylcholine esterase inhibitor poisoning from a home-made shampoo.

PubMed

Sadaka, Yair; Broides, Arnon; Tzion, Raffi Lev; Lifshitz, Matitiahu

2011-07-01

Organophosphate acetylcholine esterase inhibitor poisoning is a major health problem in children. We report an unusual cause of organophosphate acetylcholine esterase inhibitor poisoning. Two children were admitted to the pediatric intensive care unit due to organophosphate acetylcholine esterase inhibitor poisoning after exposure from a home-made shampoo that was used for the treatment of head lice. Owing to no obvious source of poisoning, the diagnosis of organophosphate acetylcholine esterase inhibitor poisoning in one of these patients was delayed. Both patients had an uneventful recovery. Organophosphate acetylcholine esterase inhibitor poisoning from home-made shampoo is possible. In cases where the mode of poisoning is unclear, direct questioning about the use of home-made shampoo is warranted, in these cases the skin and particularly the scalp should be rinsed thoroughly as soon as possible.

The Novaco Anger Scale-Provocation Inventory (1994 version) in Dutch forensic psychiatric patients.

PubMed

Hornsveld, Ruud H J; Muris, Peter; Kraaimaat, Floris W

2011-12-01

We examined the psychometric properties of the Novaco Anger Scale-Provocation Inventory (NAS-PI, 1994 version) in Dutch violent forensic psychiatric patients and secondary vocational students. A confirmatory factor analysis of the subscale structure of the NAS was carried out, reliability was investigated, and relations were calculated between NAS-PI scores and other measures of personality traits and problem behaviors. The 3-subscale structure of the original NAS could not be confirmed. However, the internal consistency of the NAS and the PI was excellent, and the test-retest reliability of the NAS was good. The validity of the NAS and the PI was supported by a meaningful pattern of correlations with alternative measures of anger and personality traits. Forensic psychiatric outpatients displayed higher NAS scores than secondary vocational students, but inpatients scored even lower than this nonclinical control group. Our preliminary conclusion is that the NAS-PI is a valuable instrument for the assessment of anger in Dutch violent forensic psychiatric patients.

Does response evaluation and decision (RED) mediate the relation between hostile attributional style and antisocial behavior in adolescence?

PubMed

Fontaine, Reid Griffith; Tanha, Marieh; Yang, Chongming; Dodge, Kenneth A; Bates, John E; Pettit, Gregory S

2010-07-01

The role of hostile attributional style (HAS) in antisocial development has been well-documented. We analyzed longitudinal data on 585 youths (48% female; 19% ethnic minority) to test the hypothesis that response evaluation and decision (RED) mediates the relation between HAS and antisocial behavior in adolescence. In Grades 10 and 12, adolescent participants and their parents reported participants' antisocial conduct. In Grade 11, participants were asked to imagine themselves in videotaped ambiguous-provocation scenarios. Segment 1 of each scenario presented an ambiguous provocation, after which participants answered HAS questions. In segment 2, participants were asked to imagine themselves responding aggressively to the provocateur, after which RED was assessed. Structural equation modeling indicated that RED mediates the relation between HAS and subsequent antisocial conduct, controlling for previous misconduct. Findings are consistent with research on the development of executive function processes in adolescence, and suggest that the relation between HAS and RED changes after childhood.

Does Response Evaluation and Decision (RED) Mediate the Relation between Hostile Attributional Style and Antisocial Behavior in Adolescence?

PubMed Central

Tanha, Marieh; Yang, Chongming; Dodge, Kenneth A.; Bates, John E.; Pettit, Gregory S.

2013-01-01

The role of hostile attributional style (HAS) in antisocial development has been well-documented. We analyzed longitudinal data on 585 youths (48% female; 19% ethnic minority) to test the hypothesis that response evaluation and decision (RED) mediates the relation between HAS and antisocial behavior in adolescence. In Grades 10 and 12, adolescent participants and their parents reported participants’ antisocial conduct. In Grade 11, participants were asked to imagine themselves in videotaped ambiguous-provocation scenarios. Segment 1 of each scenario presented an ambiguous provocation, after which participants answered HAS questions. In segment 2, participants were asked to imagine themselves responding aggressively to the provocateur, after which RED was assessed. Structural equation modeling indicated that RED mediates the relation between HAS and subsequent antisocial conduct, controlling for previous misconduct. Findings are consistent with research on the development of executive function processes in adolescence, and suggest that the relation between HAS and RED changes after childhood. PMID:20186477

Comparison of Valsalva Maneuver, Amyl Nitrite, and Exercise Echocardiography to Demonstrate Latent Left Ventricular Outflow Obstruction in Hypertrophic Cardiomyopathy.

PubMed

Ayoub, Chadi; Geske, Jeffrey B; Larsen, Carolyn M; Scott, Christopher G; Klarich, Kyle W; Pellikka, Patricia A

2017-12-15

Guidelines recommend exercise stress echocardiogram (ESE) for patients with hypertrophic cardiomyopathy (HC) if a 50 mm Hg gradient is not present at rest or provoked with Valsalva or amyl nitrite, to direct medical and surgical management. However, no study has directly compared all 3 methods. We sought to evaluate efficacy and degree of provocation of left ventricular outflow gradients by ESE, and compare with Valsalva and amyl nitrite. In patients with HC between 2002 and 2015, resting echocardiograms and ESEs within 1 year were retrospectively reviewed. Gradients elicited by each provocation method were compared. Rest and ESE were available in 97 patients (mean age 54 ± 18 years, 57% male); 78 underwent Valsalva maneuver and 41 amyl nitrite provocation. Median gradients (interquartile range) were 10 mm Hg (7,19) at rest, 16 mm Hg (9,34) with Valsalva, 23 mm Hg (13,49) with amyl nitrite, and 26 mm Hg (13,58) with ESE. ESE and amyl nitrite were able to provoke obstruction (≥30 mm Hg) and severe obstruction (≥50 mm Hg) more frequently than Valsalva. In patients with resting gradient <30 mm Hg (n = 83), provocation maneuvers demonstrated dynamic obstruction in 51%; in those with Valsalva gradient <30 mm Hg (n = 57), ESE or amyl nitrite provoked a gradient in 44%; and in those with amyl nitrite gradient <30 mm Hg (n = 20), ESE provoked a gradient in 29%. No demographic or baseline echocardiographic parameter predicted provocable obstruction. In conclusion, ESE is clinically useful; however, different provocation maneuvers may be effective in different patients with HC, and all maneuvers may be required to provoke dynamic obstruction in symptomatic patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Non-immediate reactions to beta-lactams: diagnostic value of skin testing and drug provocation test.

PubMed

Padial, A; Antunez, C; Blanca-Lopez, N; Fernandez, T D; Cornejo-Garcia, J A; Mayorga, C; Torres, M J; Blanca, M

2008-05-01

beta-Lactam (BL) antibiotics can induce non-immediate skin reactions, frequently manifested as exanthema or urticaria. The time between drug intake and the reaction appearance is generally 24-48 h. Because the mechanisms involved are not completely understood, diagnostic tests for these reactions have still to be fully validated. To evaluate the role of skin and drug provocation tests (DPTs) in the diagnosis of patients with non-immediate reactions to BL. We evaluated a group of 22 patients who developed maculopapular exanthema or urticarial exanthema after BL intake. Diagnosis was confirmed by DPT with BL. Intradermal/patch testing was performed with benzylpenicilloyl, minor determinant mixture, amoxicillin (AX), ampicillin (AMP) and the culprit drug in patients and in 22 negative controls. Immunohistochemical studies were done in the affected skin at the acute phase of the reaction and after a delayed positive skin test/DPT. IFN-gamma and IL-4 were quantified in peripheral mononuclear cells, obtained during the positive response to DPT and after resolution of the symptoms. From the total number of cases, 12 patients developed urticarial exanthema and 10 maculopapular exanthema after DPT. Only two of the 22 patients (9%) had a positive delayed intradermal skin test: one to AX/AMP and the other to cloxacillin. Biopsies showed a mononuclear CD4, CD8 infiltrate and activated and memory cells. The cytokine expression showed a Th1 pattern in patients, in contrast with the Th0 pattern in controls. In patients with non-immediate reactions to BLs (maculopapular exathema or urticarial exanthema), the sensitivity of skin testing is low and DPT may be required to establish the diagnosis. The reproducibility of the reactions and the cytokine pattern expressed during the acute episode support a T cell-induced non-immediate response.

A comparison of skin endpoint titration and skin-prick testing in the diagnosis of allergic rhinitis.

PubMed

Gungor, Anil; Houser, Steven M; Aquino, Benjamin F; Akbar, Imran; Moinuddin, Rizwan; Mamikoglu, Bulent; Corey, Jacquelynne P

2004-01-01

Among the many methods of allergy diagnosis are intradermal testing (IDT) and skin-prick testing (SPT). The usefulness of IDT has been called into question by some authors, while others believe that studies demonstrating that SPT was superior might have been subject to bias. We conducted a study to compare the validity of SPT and IDT--specifically, the skin endpoint titration (SET) type of IDT--in diagnosing allergic rhinitis. We performed nasal provocation testing on 62 patients to establish an unbiased screening criterion for study entry. Acoustic rhinometric measurements of the nasal responses revealed that 34 patients tested positive and 28 negative. All patients were subsequently tested by SET and SPT. We found that SPT was more sensitive (85.3 vs 79.4%) and more specific (78.6 vs 67.9%) than SET as a screening procedure. The positive predictive value of SPT was greater than that of SET (82.9 vs 75.0%), as was the negative predictive value (81.5 vs 73.0%). None of these differences was statistically significant; because of the relatively small sample size, our study was powered to show only equivalency. The results of our study suggest that the information obtained by the SET method of IDT is comparable to that obtained by SPT in terms of sensitivity, specificity, and overall performance and that both SET and SPT correlate well with nasal provocation testing for ragweed. Therefore, the decision as to which to use can be based on other factors, such as the practitioner's training, the desire for quantitative results, the desire for rapid results, and the type of treatment (i.e., immunotherapy or pharmacotherapy) that is likely to be chosen on the basis of test results.

Ranitidine-induced anaphylaxis: clinical features, cross-reactivity, and skin testing.

PubMed

Park, K H; Pai, J; Song, D-G; Sim, D W; Park, H J; Lee, J-H; Jeong, K Y; Pan, C-H; Shin, I; Park, J-W

2016-04-01

Histamine H2 receptor antagonists are commonly prescribed medications and are known to be well tolerated. However, 99 cases of ranitidine-induced anaphylaxis occurred in Korea from 2007 to 2014. The purpose of this study was to determine the incidence, clinical features, and diagnostic methods for ranitidine-induced anaphylaxis. Ranitidine-related pharmacovigilance data from 2007 to 2014 were reviewed. Adverse drug reactions with causal relationships were selected, and clinical manifestations, outcomes, and drug-related information were assessed. For further investigation, 8 years of pharmacovigilance data were collected at a single centre. Twenty-three patients participated in in vivo and in vitro studies. Skin tests, oral provocation tests, and laboratory tests were performed, including tests using other kinds of histamine H2 receptor antagonists. Over 7 years, 584 patients suffered adverse reactions to ranitidine. The most common manifestation was cutaneous symptoms. Among them, 99 patients (17.0%) experienced anaphylaxis. In a single-centre study, skin prick tests were positive in 91.7% of ranitidine-induced anaphylaxis patients (11/12); the optimal concentration was 20 mg/mL. Detection of ranitidine-specific immunoglobulin E failed. Cimetidine and proton pump inhibitors showed no cross-reactivity with ranitidine based on the skin prick test, oral provocation test, or clinical determination. Surprisingly, 82.6% of patients reintroduced ranitidine and re-experienced the same adverse reactions because ranitidine was not considered the culprit drug. Although ranitidine is known as a safe drug, it can also cause diverse adverse reactions, including anaphylaxis. This study demonstrates the need to pay attention to adverse reactions to ranitidine and consider ranitidine as a cause of anaphylaxis. © 2016 John Wiley & Sons Ltd.

Changes in Extracellular Striatal Acetylcholine and Brain Seizure Activity Following Acute Exposure to Nerve Against in Freely Moving Guinea Pigs

DTIC Science & Technology

2010-01-01

Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Changes in extracellular striatal acetylcholine and brain seizure activity following...Acetylcholine, acetylcholinesterase, choline, guinea pig, in vivo microdialysis, nerve agents, organophosphorus compounds, sarin, seizure activity ...RESEARCH ARTICLE Changes in extracellular striatal acetylcholine and brain seizure activity following acute exposure to nerve agents in freely

Occupational asthma due to soft corrosive soldering fluxes containing zinc chloride and ammonium chloride.

PubMed Central

Weir, D C; Robertson, A S; Jones, S; Burge, P S

1989-01-01

Two cases of occupational asthma due to soft corrosive soldering fluxes used in metal jointing are described in which the diagnosis was based on work related deterioration in daily peak expiratory flow rate and positive responses in bronchial provocation tests. Both fluxes contained ammonium chloride and zinc chloride. Occupational asthma provoked by these agents has not previously been reported. PMID:2705153

In silico screening of the impact of hERG channel kinetic abnormalities on channel block and susceptibility to acquired long QT syndrome

PubMed Central

Romero, Lucia; Trenor, Beatriz; Yang, Pei-Chi; Saiz, Javier; Clancy, Colleen E.

2014-01-01

Accurate diagnosis of predisposition to long QT syndrome is crucial for reducing the risk of cardiac arrhythmias. In recent years, drug-induced provocative tests have proved useful to unmask some latent mutations linked to cardiac arrhythmias. In this study we expanded this concept by developing a prototype for a computational provocative screening test to reveal genetic predisposition to acquired Long-QT Syndrome (aLTQS). We developed a computational approach to reveal the pharmacological properties of IKr blocking drugs that are most likely to cause aLQTS in the setting of subtle alterations in IKr channel gating that would be expected to result from benign genetic variants. We used the model to predict the most potentially lethal combinations of kinetic anomalies and drug properties. In doing so, we also implicitly predicted ideal inverse therapeutic properties of K channel openers that would be expected to remedy a specific defect. We systematically performed “in silico mutagenesis” by altering discrete kinetic transition rates of the Fink et al. Markov model of human IKr channels, corresponding to activation, inactivation, deactivation and recovery from inactivation of IKr channels. We then screened and identified the properties of IKr blockers that caused acquired Long QT and therefore unmasked mutant phenotypes for mild, moderate and severe variants. Mutant IKr channels were incorporated into the O’Hara et al. human ventricular action potential (AP) model and subjected to simulated application of a wide variety of IKr-drug interactions in order to identify the characteristics that selectively exacerbate the AP duration (APD) differences between wild-type and IKr mutated cells. Our results show that drugs with disparate affinities to conformation states of the IKr channel are key to amplify variants underlying susceptibility to acquired Long QT Syndrome, an effect that is especially pronounced at slow frequencies. Finally, we developed a mathematical formulation of the M54T MiRP1 latent mutation and simulated a provocative test. In this setting, application of dofetilide dramatically amplified the predicted QT interval duration in the M54T hMiRP1 mutation compared to wild-type. PMID:24631769

Stimulation of the Nonneuronal Cholinergic System by Highly Diluted Acetylcholine in Keratinocytes.

PubMed

Uberti, Francesca; Bardelli, Claudio; Morsanuto, Vera; Ghirlanda, Sabrina; Cochis, Andrea; Molinari, Claudio

2017-01-01

The physiological effects of acetylcholine on keratinocytes depend on the presence of nicotinic and muscarinic receptors. The role of nonneuronal acetylcholine in keratinocytes could have important clinical implications for patients with various skin disorders such as nonhealing wounds. In order to evaluate the efficacy of highly diluted acetylcholine solutions obtained by sequential kinetic activation, we aimed to investigate the effects of these solutions on normal human keratinocytes. Two different concentrations (10 fg/mL and 1 pg/mL) and formulations (kinetically activated and nonkinetically activated) of acetylcholine were used to verify keratinocyte viability, proliferation, and migration and the intracellular pathways involved using MTT, crystal violet, wound healing, and Western blot compared to 147 ng/mL acetylcholine. The activated formulations (1 pg/mL and 10 fg/mL) revealed a significant capacity to increase migration, cell viability, and cell proliferation compared to 147 ng/mL acetylcholine, and these effects were more evident after a single administration. Sequential kinetic activation resulted in a statistically significant decrease in reactive oxygen species production accompanied by an increase in mitochondrial membrane potential and a decrease in oxygen consumption compared to 147 ng/mL acetylcholine. The M1 muscarinic receptor was involved in these effects. Finally, the involvement of ERK/mitogen-activated protein kinases (MAPK) and KI67 confirmed the effectiveness of the single treatment on cell proliferation. The intracellular pathways of calcium were investigated as well. Our results indicate for the first time that highly diluted and kinetically activated acetylcholine seems to play an active role in an in vitro model of wound healing. Moreover, the administration of acetylcholine within the physiological range may not only be effective but is also likely to be safe. © 2016 S. Karger AG, Basel.

Choline acetyltransferase and organic cation transporters are responsible for synthesis and propionate-induced release of acetylcholine in colon epithelium.

PubMed

Bader, Sandra; Klein, Jochen; Diener, Martin

2014-06-15

Acetylcholine is not only a neurotransmitter, but is found in a variety of non-neuronal cells. For example, the enzyme choline acetyltransferase (ChAT), catalyzing acetylcholine synthesis, is expressed by the colonic epithelium of different species. These cells release acetylcholine across the basolateral membrane after luminal exposure to propionate, a short-chain fatty acid. The functional consequence is the induction of chloride secretion, measurable as increase in short-circuit current (Isc) in Ussing chamber experiments. It is unclear how acetylcholine is produced and released by colonic epithelium. Therefore, the aim of the present study was the identification (on mRNA and protein level) and functional characterization (in Ussing chamber experiments combined with HPLC detection of acetylcholine) of transporters/enzymes in the cholinergic system of rat colonic epithelium. Immunohistochemical staining as well as RT-PCR revealed the expression of high-affinity choline transporter, ChAT, carnitine acetyltransferase (CarAT), vesicular acetylcholine transporter (VAChT), and organic cation transporters (OCT 1, 2, 3) in colonic epithelium. In contrast to blockade of ChAT with bromoacetylcholine, inhibition of CarAT with mildronate did not inhibit the propionate-induced increase in Isc, suggesting a predominant synthesis of epithelial acetylcholine by ChAT. Although being expressed, blockade of VAChT with vesamicol was ineffective, whereas inhibition of OCTs with omeprazole and corticosterone inhibited propionate-induced Isc and the release of acetylcholine into the basolateral compartment. In summary, OCTs seem to be involved in regulated acetylcholine release by colonic epithelium, which is assumed to be involved in chemosensing of luminal short-chain fatty acids by the intestinal epithelium. Copyright © 2014 Elsevier B.V. All rights reserved.

Exercise and neuromodulators: choline and acetylcholine in marathon runners

NASA Technical Reports Server (NTRS)

Conlay, L. A.; Sabounjian, L. A.; Wurtman, R. J.

1992-01-01

Certain neurotransmitters (i.e., acetylcholine, catecholamines, and serotonin) are formed from dietary constituents (i.e., choline, tyrosine and tryptophan). Changing the consumption of these precursors alters release of their respective neurotransmitter products. The neurotransmitter acetylcholine is released from the neuromuscular junction and from brain. It is formed from choline, a common constituent in fish, liver, and eggs. Choline is also incorporated into cell membranes; membranes may likewise serve as an alternative choline source for acetylcholine synthesis. In trained athletes, running a 26 km marathon reduced plasma choline by approximately 40%, from 14.1 to 8.4 uM. Changes of similar magnitude have been shown to reduce acetylcholine release from the neuromuscular junction in vivo. Thus, the reductions in plasma choline associated with strenuous exercise may reduce acetylcholine release, and could thereby affect endurance or performance.

The challenges of modulating the 'rest and digest' system: acetylcholine receptors as drug targets.

PubMed

VanPatten, Sonya; Al-Abed, Yousef

2017-01-01

Acetylcholine, a major neurotransmitter of the parasympathetic and sympathetic nervous systems, was discovered in the early 1900s. Over the years, researchers have revealed much about its regulation, properties of its receptors and features of the downstream signaling that influence its terminal effects. The acetylcholine system, traditionally associated with neuromuscular communication, is now known to play a crucial part in modulation of the immune system and other 'rest and digest' effects. Recent research seeks to elucidate the system's role in brain functions including cognition, sleep, arousal, motivation, reward and pain. We highlight clinically approved and experimental drugs that modulate the acetylcholine receptors. The complexities in targeting the acetylcholine receptors are vast and finding future indications for drug development associated with specific acetylcholine receptors remains a challenge. Copyright © 2016 Elsevier Ltd. All rights reserved.

Organophosphate acetylcholine esterase inhibitor poisoning from a home-made shampoo

PubMed Central

Sadaka, Yair; Broides, Arnon; Tzion, Raffi Lev; Lifshitz, Matitiahu

2011-01-01

Organophosphate acetylcholine esterase inhibitor poisoning is a major health problem in children. We report an unusual cause of organophosphate acetylcholine esterase inhibitor poisoning. Two children were admitted to the pediatric intensive care unit due to organophosphate acetylcholine esterase inhibitor poisoning after exposure from a home-made shampoo that was used for the treatment of head lice. Owing to no obvious source of poisoning, the diagnosis of organophosphate acetylcholine esterase inhibitor poisoning in one of these patients was delayed. Both patients had an uneventful recovery. Organophosphate acetylcholine esterase inhibitor poisoning from home-made shampoo is possible. In cases where the mode of poisoning is unclear, direct questioning about the use of home-made shampoo is warranted, in these cases the skin and particularly the scalp should be rinsed thoroughly as soon as possible. PMID:21887044

Experimental pain in the groin may refer into the lower abdomen: Implications to clinical assessments.

PubMed

Drew, M K; Palsson, T S; Hirata, R P; Izumi, M; Lovell, G; Welvaert, M; Chiarelli, P; Osmotherly, P G; Graven-Nielsen, T

2017-10-01

To investigate the effects of experimental adductor pain on the pain referral pattern, mechanical sensitivity and muscle activity during common clinical tests. Repeated-measures design. In two separate sessions, 15 healthy males received a hypertonic (painful) and isotonic (control) saline injection to either the adductor longus (AL) tendon to produce experimental groin pain or into the rectus femoris (RF) tendon as a painful control. Pain intensity was recorded on a visual analogue scale (VAS) with pain distribution indicated on body maps. Pressure pain thresholds (PPT) were assessed bilaterally in the groin area. Electromyography (EMG) of relevant muscles was recorded during six provocation tests. PPT and EMG assessment were measured before, during and after experimental pain. Hypertonic saline induced higher VAS scores than isotonic saline (p<0.001), and a local pain distribution in 80% of participants. A proximal pain referral to the lower abdominal region in 33% (AL) and 7% (RF) of participants. Experimental pain (AL and RF) did not significantly alter PPT values or the EMG amplitude in groin or trunk muscles during provocation tests when forces were matched with baseline. This study demonstrates that AL tendon pain was distributed locally in the majority of participants but may refer to the lower abdomen. Experimental adductor pain did not significantly alter the mechanical sensitivity or muscle activity patterns. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Correlation of clinical examination characteristics with three sources of chronic low back pain.

PubMed

Young, Sharon; Aprill, Charles; Laslett, Mark

2003-01-01

Research has demonstrated some progress in using a clinical examination to predict discogenic or sacroiliac (SI) joint sources of pain. No clear predictors of symptomatic lumbar zygapophysial joints have yet been demonstrated. To identify significant components of a clinical examination that are associated with symptomatic lumbar discs, zygapophysial joints and SI joints. A prospective, criterion-related concurrent validity study performed at a private radiology practice specializing in spinal diagnostics. The sample consisted of 81 patients with chronic lumbopelvic pain referred for diagnostic injections. Contingency tables were constructed for nine features of the clinical evaluation compared with the results of diagnostic injections. Statistical analysis included chi-squared test for independence, phi and odds ratios with confidence intervals. Patients received blinded clinical examinations by physical therapists, and diagnostic injections were used as the criterion standard. Significant relationships were found between discogenic pain and centralization of pain during repeated movement testing, and pain when rising from sitting. Lumbar zygapophysial joint pain was associated with absence of pain when rising from sitting. Sacroiliac joint pain was related to three or more positive pain provocation tests, pain when rising from sitting, unilateral pain and absence of lumbar pain. Significant correlations exist between clinical examination findings and symptomatic lumbar discs, zygapophysial and SI joints. The strongest relationships were seen between SI joint pain and three or more positive pain provocation tests, centralization of pain for symptomatic discs and absence of pain when rising from sitting for symptomatic lumbar zygapophysial joints.

The Oral Provocation Test for Raw Egg in Patients with Hen Egg Allergy.

PubMed

Kido, Jun; Nishi, Natsuko; Matsumoto, Tomoaki

2018-06-06

Many researchers have made efforts to develop diagnostic tools for predicting the outcome of oral food challenges (OFCs). The aim of this study was to assess the diagnostic value of the skin prick test (SPT) and blood-specific IgE concentrations based on the outcome of the OFCs for heated and raw hen egg. This study included 103 children with suspected hen egg allergy (HEA; median age 23 months, range 10-155; 72 boys, 31 girls). Forty-three patients were diagnosed with HEA by OFC. Of 60 patients who tolerated heated egg white (HEW), 22 underwent the OFC for raw hen egg and 7 developed adverse reactions after ingesting raw egg. Their wheal diameters and specific IgE levels for egg white and ovomucoid were determined. Wheal diameters as well as blood-specific IgE levels for egg white and ovomucoid were significantly larger in children with positive OFC results for HEW than in those with negative results. However, there were no significant differences between the positive and negative test results for raw hen egg white (REW) in wheal diameter or blood-specific IgE levels. The SPT and blood-specific IgE can be used to diagnose HEA. However, the provocation test for REW in children without HEW allergy is important because the values of SPT and specific IgE were not significantly different between children with and without raw egg allergy. © 2018 S. Karger AG, Basel.

Transient neonatal myasthenia gravis due to a mother with ocular onset of anti-muscle specific kinase myasthenia gravis.

PubMed

Lee, Ju-Yeun; Min, Ju-Hong; Han, Sueng-Han; Han, Jinu

2017-07-01

We describe a 27-year-old pregnant female with new onset of conjugate gaze deficit during the third trimester of pregnancy. Repetitive nerve stimulation tests, neostigmine tests, and acetylcholine receptor antibody assays were all negative. The patient delivered a normal healthy baby at a local clinic via cesarean section. The baby became hypotonic and had respiratory failure several minutes after birth. The result of acetylcholine receptor antibody was negative in the neonate. The neonate became healthy spontaneously and was extubated after 21 days of ventilation care. Two months after delivery, the mother developed ptosis and generalized symptoms and subsequent workup revealed she was muscle specific kinase (MuSK) antibody positive. The neonate was presumed to have an anti-MuSK-mediated transient neonatal myasthenia gravis. Although MuSK antibody testing is rarely indicated in ocular myasthenia gravis, MuSK antibody testing is necessary in pregnant women who are presumed ocular myasthenia gravis to warn occurrence of transient neonatal myasthenia gravis. Copyright © 2017 Elsevier B.V. All rights reserved.

Return to Flying Duties Following Centrifuge or Vibration Exposures

NASA Technical Reports Server (NTRS)

Scheuring, Richard A.; Clarke, Jonathan; Jones, Jeffrey A.

2009-01-01

Introduction: In an effort to determine the human performance limits for vibration in spacecraft being developed by NASA, astronauts were evaluated during a simulated launch profile in a centrifuge/vibration environment and separate vibration-only simulation. Current USAF and Army standards for return to flight following centrifuge exposures require 12-24 hours to pass before a crewmember may return to flying duties. There are no standards on vibration exposures and return to flying duties. Based on direct observation and provocative neurological testing of the astronauts, a new standard for return to flying duties following centrifuge and/or vibration exposures was established. Methods: 13 astronaut participants were exposed to simulated launch profiles in a + 3.5 Gx bias centrifuge/vibration environment and separately on a vibration table at the NASA-Ames Research Center. Each subject had complete neurological evaluations pre- and post-exposure for the centrifuge/vibration runs with the NASA neurological function rating scale (NFRS). Subjects who participated in the vibration-only exposures had video oculography performed with provocative maneuvers in addition to the NFRS. NFRS evaluations occurred immediately following each exposure and at 1 hour post-run. Astronauts who remained symptomatic at 1 hour had repeat NFRS performed at 1 hour intervals until the crewmember was asymptomatic. Results: Astronauts in the centrifuge/vibration study averaged a 3-5 point increase in NFRS scores immediately following exposure but returned to baseline 3 hours post-run. Subjects exposed to the vibration-only simulation had a 1-3 point increase following exposure and returned to baseline within 1-2 hours. Pre- and post- vibration exposure video oculography did not reveal any persistent ocular findings with provocative testing 1 hour post-exposure. Discussion: Based on direct observations and objective measurement of neurological function in astronauts following simulated launch profiles, asymptomatic individuals are allowed to return to flying duties within 3 hours following centrifuge/vibration and 2 hours after vibration-only exposures.

Clinical relevance of syncope and presyncope induced by tilt testing.

PubMed

Zyśko, Dorota; Gajek, Jacek; Koźluk, Edward; Agrawal, Anil Kumar; Smereka, Jacek; Checiński, Igor

2009-08-01

The authors investigated the relation between presyncope and syncope induced by tilt testing (HUTT) and demographics, medical history and HUTT data.The demographics, syncopal burden, data regarding the spontaneous syncope and reproduction of symptoms during HUTT were compared among patients with induced syncope and presyncope. The study group consisted of 574 patients (371 women, 203 men), aged 43.7 +/- 18.5 years. Patients with syncope induced by HUTT (418 patients, 63.9% women) had a higher number of syncopal episodes in their medical history. Stepwise logistic regression revealed that syncope provocation was independently related to the cardiodepressive type of neurocardiogenic reaction (OR 7.8, CI 4.2-14.4, P < 0.001), NTG use (OR 1.7, CI: 1.0-2.7, P < 0.05), the reproduction of the symptoms during HUTT (OR 2.0, CI: 1.3-3.1, P < 0.01) and the higher number of syncopal episodes (OR 2.0, CI: 1.3-3.0, P < 0.01). In patients with positive HUTT during a passive phase it was related to the cardiodepressive type of reaction (OR 26.5, CI: 5.9-118.5, P < 0.001). In the group with positive HUTT after NTG syncope was related to the cardiodepressive type (OR 5.7, CI: 2.9-11.2, P < 0.001), vasovagal history (OR 2.0, CI: 1.2-3.3, P < 0.01), reproduction of the spontaneous symptoms (OR 1.9, CI: 1.1-3.1, P < 0.05) and higher number of syncopal episodes (OR 2.1, CI: 1.3-3.3, P < 0.01). Syncope is more frequently a HUTT outcome than presyncope. The provocation of syncope in the passive phase of HUTT depends only on the cardiodepressive type of neurocardiogenic reaction. The induction of presyncope after nitroglycerin provocation is related to the possibility of a false positive reaction.

Individual Differences in Responses to Provocation and Frequent Victimization by Peers

ERIC Educational Resources Information Center

Champion, Kelly M.; Clay, Daniel L.

2007-01-01

This study examined associations between victimization by peers and intention to respond to provocative events as a function of anger arousal and motivation to improve the situation in a cross-sectional sample of school-age children (N = 506, 260 males, 246 females). Results demonstrated that more intense anger and more retaliatory motivation were…

Children's Emotion Regulation: Self-Report and Physiological Response to Peer Provocation

ERIC Educational Resources Information Center

Hessler, Danielle M.; Katz, Lynn Fainsilber

2007-01-01

The authors examined the notion that children's emotion regulation (ER) is a uniform skill by (a) investigating the concordance between self-report of ER and physiological measures and by (b) examining ER in a specific context (e.g., peer provocation) and context-free manner (e.g., during a semistructured interview of ER abilities). Seventy-two…

The Photomontages of John Heartfield: A Provocative Teaching Tool for "Landeskunde."

ERIC Educational Resources Information Center

Mathieu, Gustave Bording

1992-01-01

A case is made for the use of the politically provocative photomontages of Heartfield (a.k.a. Berlin-born Helmut Herzfeld) in the German classroom. The interplay of language, art, culture, and history makes them especially useful as realia. A model for teaching them is presented, including a chronology and nine reproductions. (Author/LB)

Oxotremorine does not enhance acetylcholine release from rat diaphragm preparations.

PubMed Central

Gundersen, C. B.; Jenden, D. J.

1980-01-01

We have reinvestigated the dramatic effect of oxotremorine on acetylcholine release from the rat diaphragm reported by Das, Ganguly & Vedasiromoni (1978), using a rigorous gas chromatographic mass spectrometric/isotope dilution method for identification and measurement of acetylcholine and choline. Oxotremorine (10 microM) causes no significant change in the spontaneous or evoked (1 or 10 Hz) release or in the tissue levels of acetylcholine or choline. PMID:7426831

Why we forget our dreams: Acetylcholine and norepinephrine in wakefulness and REM sleep.

PubMed

Becchetti, Andrea; Amadeo, Alida

2016-01-01

The ascending fibers releasing norepinephrine and acetylcholine are highly active during wakefulness. In contrast, during rapid-eye-movement sleep, the neocortical tone is sustained mainly by acetylcholine. By comparing the different physiological features of the norepinephrine and acetylcholine systems in the light of the GANE (glutamate amplifies noradrenergic effects) model, we suggest how to interpret some functional differences between waking and rapid-eye-movement sleep.

Deanol and methylphenidate in minimal brain dysfunction.

PubMed

Lewis, J A; Young, R

1975-05-01

Deanol, a putative acetylcholine precursor, has been used as a treatment for childhood hyperactivity for years. Efficacy has not been satisfactorily established, however. Seventy-four children referred for problems with learning, including many with hyperactivity, were screened for neurological or psychiatric illness, then given deanol, methylphenidate, or placebo in a double-blind fashion for 3 months. Maintenance dose for methylphenidate was 40 mg daily; for deanol, 500 mg. Behavior rating forms, reaction time, and a series of standard psychometric tests were given before and after treatment. Both drugs showed significant improvement on a number of tests; the pattern and degree of change differed slightly for the two. In this paradigm, deanol thus appeared to improve performance in children with learning and behavior disorders. The mechanism of action remains speculative; proof that deanol increases acetylcholine is scanty, and there is a theoretical basis for actually assuming an anticholinergic effect. Further clinical studies on deanol are indicated.

Both substance P agonists and antagonists inhibit ion conductance through nicotinic acetylcholine receptors on PC12 cells.

PubMed

Eardley, D; McGee, R

1985-08-07

Substance P stimulates substance P receptors but also inhibits ion conductance through nicotinic acetylcholine receptors. Substance P analogs, classified as agonists or antagonists based on their actions on smooth muscle, were tested to determine if they also could act at nicotinic receptors on the pheochromocytoma, PC12. All of the analogs tested, [D-Pro2, D-Trp7,9]SP, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP, [pGlu5, MePhe8, Sar9]SP-(5-11), and [D-Pro4, D-Trp7,9,10]SP-(4-11), inhibited agonist-induced uptake of 86Rb+ through the nicotinic receptors at concentrations quite similar to those required for action at substance P receptors on smooth muscle. Thus, the chemical modifications in the analogs do not substantially alter their ability to inhibit nicotinic receptors.

Back to the future: Rational maps for exploring acetylcholine receptor space and time.

PubMed

Tessier, Christian J G; Emlaw, Johnathon R; Cao, Zhuo Qian; Pérez-Areales, F Javier; Salameh, Jean-Paul J; Prinston, Jethro E; McNulty, Melissa S; daCosta, Corrie J B

2017-11-01

Global functions of nicotinic acetylcholine receptors, such as subunit cooperativity and compatibility, likely emerge from a network of amino acid residues distributed across the entire pentameric complex. Identification of such networks has stymied traditional approaches to acetylcholine receptor structure and function, likely due to the cryptic interdependency of their underlying amino acid residues. An emerging evolutionary biochemistry approach, which traces the evolutionary history of acetylcholine receptor subunits, allows for rational mapping of acetylcholine receptor sequence space, and offers new hope for uncovering the amino acid origins of these enigmatic properties. Copyright © 2017 Elsevier B.V. All rights reserved.

Interactions between oxiracetam, aniracetam and scopolamine on behavior and brain acetylcholine.

PubMed

Spignoli, G; Pepeu, G

1987-07-01

The effect of cognition-enhancing agents oxiracetam and aniracetam on scopolamine-induced amnesia and brain acetylcholine decrease was investigated in the rat. Acetylcholine levels were measured by means of a gas-chromatographic method. Scopolamine (0.63 mg/kg IP 60 min before training) prevented the acquisition of a passive avoidance conditioned response ("step through": retest 30 min after training) and brought about a 64, 56 and 42% decrease in acetylcholine level in the cortex, hippocampus and striatum respectively. Oxiracetam (50 and 100 mg/kg IP) administered 30 min before scopolamine reduced the scopolamine-induced amnesic effect and decrease in acetylcholine level in the cortex and hippocampus, but not in the striatum. Lower and higher doses of oxiracetam were ineffective. Aniracetam (100 mg/kg PO) also prevented scopolamine-induced amnesia but attenuated acetylcholine decrease in the hippocampus only. Aniracetam (300 mg PO) reduced acetylcholine decrease in the hippocampus but did not prevent scopolamine-amnesia. In conclusion, oxiracetam and aniracetam exert a stimulatory effect on specific central cholinergic pathways. However, a direct relationship between cognition-enhancing properties and cholinergic activation needs further confirmation.

Electrolyte and protein secretion by the perfused rabbit mandibular gland stimulated with acetylcholine or catecholamines

PubMed Central

Case, R. M.; Conigrave, A. D.; Novak, I.; Young, J. A.

1980-01-01

1. A method is described for the isolation and vascular perfusion in vitro of the mandibular gland of the rabbit. The perfusate is a physiological salt solution containing glucose as the only metabolic substrate. 2. During perfusion with solutions containing acetylcholine, the gland secretes vigorously at a rate and in a manner similar to that seen in vivo. Although the gland becomes oedematous during perfusion, the extent of this oedema appears to have no influence on secretory ability: the perfused glands were capable of functioning for at least 4 h, and often for more than 6 h. 3. Acetylcholine evoked a small secretory response at a concentration of 8 × 10-9 mol l-1 and a maximum response at 8 × 10-7 mol l-1. Eserine (2 × 10-5 mol l-1) evoked secretory responses comparable to those evoked by acetylcholine in a concentration of 8 × 10-9 mol l-1. Secretion, whether unstimulated or evoked by acetylcholine or eserine, could be blocked completely by atropine. 4. During prolonged stimulation with acetylcholine, the fluid secretory response declined rapidly over a period of about 15 min from an initial high value to a much lower plateau value. After 3 or more hours of stimulation, the secretory response began once more to decline, this time towards zero. If, before the second period of decline begins, stimulation is interrupted for about 30 min, the gland recovers its initial responsiveness to further stimulation with acetylcholine. 5. The Na, K, Cl and HCO3 concentrations and the osmolality of acetylcholine evoked saliva exhibited flow-dependency similar to that seen in vivo. The concentrations of Na and Cl, but not K and HCO3, increased by about 25 mmol l-1 during periods of prolonged stimulation with acetylcholine even though the salivary secretory rate was constant. The concentrations of K and HCO3, but not Na and Cl, increased progressively as the concentration of infused acetylcholine was increased. 6. Salivary protein secretion increased with increasing concentrations of acetylcholine to a greater extent than did fluid secretion. During continuous stimulation, the rate of protein secretion fell off much faster than the rate of fluid secretion. 7. The β-adrenergic agonist isoproterenol evoked a fluid secretory response only equal to about 5% of that evoked by acetylcholine, but still the response declined during continued stimulation. The electrolyte composition of isoproterenol-evoked saliva was vastly different from that evoked by acetylcholine, being particularly rich in K and HCO3. The isoproterenol-evoked saliva was also extremely rich in protein so that the total protein secretion evoked by isoproterenol was much greater than that evoked by acetylcholine. 8. The α-adrenergic agonist phenylephrine was without stimulatory effect on salivary fluid secretion and caused a reduction in the secretory response to acetylcholine. The drug had little or no effect on the electrolyte content of acetylcholine-evoked saliva and appeared to reduce its protein content. PMID:7381794

Effects of tryptophan depletion on selective serotonin reuptake inhibitor-remitted patients with obsessive compulsive disorder.

PubMed

Hood, Sean D; Broyd, Annabel; Robinson, Hayley; Lee, Jessica; Hudaib, Abdul-Rahman; Hince, Dana A

2017-12-01

Serotonergic antidepressants are first-line medication therapies for obsessive-compulsive disorder, however it is not known if synaptic serotonin availability is important for selective serotonin reuptake inhibitor efficacy. The present study tested the hypothesis that temporary reduction in central serotonin transmission, through acute tryptophan depletion, would result in an increase in anxiety in selective serotonin reuptake inhibitor-remitted obsessive-compulsive disorder patients. Eight patients (four males) with obsessive-compulsive disorder who showed sustained clinical improvement with selective serotonin reuptake inhibitor treatment underwent acute tryptophan depletion in a randomized, double-blind, placebo-controlled, within-subjects design, over two days one week apart. Five hours after consumption of the depleting/sham drink the participants performed a personalized obsessive-compulsive disorder symptom exposure task. Psychological responses were measured using the Spielberger State Anxiety Inventory, Yale-Brown Obsessive Compulsive Scale and Visual Analogue Scales. Free plasma tryptophan to large neutral amino acid ratio decreased by 93% on the depletion day and decreased by 1% on the sham day, as anticipated. Psychological rating scores as measured by Visual Analogue Scale showed a significant decrease in perceived control and increase in interfering thoughts at the time of provocation on the depletion day but not on the sham day. A measure of convergent validity, namely Visual Analogue Scale Similar to past, was significantly higher at the time of provocation on both the depletion and sham days. Both the depletion and time of provocation scores for Visual Analogue Scale Anxiety, Spielberger State Anxiety Inventory, Yale-Brown Obsessive Compulsive Scale and blood pressure were not significant. Acute tryptophan depletion caused a significant decrease in perceived control and increase in interfering thoughts at the time of provocation. Acute tryptophan depletion had no effect on the Spielberger State Anxiety Inventory or Visual Analogue Scale Anxiety measures, which suggests that the mechanism of action of selective serotonin reuptake inhibitors may be different to that seen in panic, social anxiety and post-traumatic stress disorder. Successful selective serotonin reuptake inhibitor treatment of obsessive-compulsive disorder may involve the ability of serotonin to switch habitual responding to goal-directed behaviour.

Visualization and functional testing of acetylcholine receptor-like molecules in cochlear outer hair cells.

PubMed

Plinkert, P K; Gitter, A H; Zimmermann, U; Kirchner, T; Tzartos, S; Zenner, H P

1990-02-01

The efferent nerve endings at outer hair cells (OHCs) have been suggested to regulate active mechanical processes in the cochlea. The discovery of acetylcholine (ACh)-producing and -degrading enzymes in these synapses gave rise to the speculation that ACh might be one of the efferent transmitters. However, there has as yet been no identification and characterization of any corresponding receptor in OHCs which is required for further clarification of this question. In the present paper existence, location and first characterization of acetylcholine receptors (AChRs) in OHCs are reported. Using two anti-AChR monoclonal antibodies, AChR epitopes were found forming a cup at the basal end of the OHCs opposite to the efferent nerve endings. Furthermore, the studied molecules could be shown to extend through the cell membrane. In addition, the denervated OHC AChR-epitopes seem to move by lateral diffusion. Application of Carbachol and ACh to the basal pole of OHCs induced a weak, reversible cell contraction. Pharmacological controls revealed, that hte motile responses were mediated by the AChRs.

Systemic Allergy to Corticosteroids: Clinical Features and Cross Reactivity.

PubMed

Barbaud, Annick; Waton, Julie

2016-01-01

Systemic hypersensitivity (HS) to corticosteroids (CS) is paradoxical but does exist. Some patients with a previous contact allergy to topical CS may develop a systemic contact dermatitis (SCD) while receiving CS orally or intravenously. However, a previous contact sensitization is not mandatory for developing a systemic HS to CS. Acute or delayed urticaria can occur in immediate HS. Immediate HS can be due to excipients, mainly carboxymethylcellulose or to CS themselves. Delayed reactions, mainly maculopapular rash and acute generalized exanthematous pustulosis can occur. Skin tests with systemic CS have to be standardized. It is necessary to determine if IDT with CS frequently induce skin atrophy or not and if such skin atrophy is transient by doing prospective studies using an standardized method and a limited injected volume (0.02 ml). Patch tests can be done in delayed HS, with readings at day 2, 4 and 7. In SCD, the Baeck's classification of CS in 3 chemical groups could explain cross reactivity between systemic CS. However, this classification is not applicable to explain cross-reactions between in systemic HS. According to the literature, 52/79 patients had a HS reaction to a group confirmed by a positive allergological investigations, but had a negative provocation test with another CS belonging to the same group. In case of non-severe cutaneous adverse reactions and when skin tests are negative, provocation tests have to be performed to find an alternative CS, even if it belongs to the same chemical group as those responsible for the initial reaction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Activation of alpha-latrotoxin receptors in neuromuscular synapses leads to a prolonged splash acetylcholine release.

PubMed

Lelyanova, V G; Thomson, D; Ribchester, R R; Tonevitsky, E A; Ushkaryov, Y A

2009-06-01

The mechanisms of acetylcholine release in presynaptic terminals of motoneurons induced by mutant alpha-latrotoxin (LT(N4C)) were analyzed. In contrast to wild-type alpha-latrotoxin that causes both continuous and splash secretion of acetylcholine and necessarity block neuromuscular transmission, LT(N4C) causes only splash release lasting over many hours. Thus, activation of alpha-latrotoxin receptors controls long-lasting enhanced secretion of acetylcholine.

Galanin antagonizes acetylcholine on a memory task in basal forebrain-lesioned rats.

PubMed

Mastropaolo, J; Nadi, N S; Ostrowski, N L; Crawley, J N

1988-12-01

Galanin coexists with acetylcholine in medial septal neurons projecting to the ventral hippocampus, a projection thought to modulate memory functions. Neurochemical lesions of the nucleus basalis-medial septal area in rats impaired choice accuracy on a delayed alternation t-maze task. Acetylcholine (7.5 or 10 micrograms intraventricularly or 1 micrograms micro-injected into the ventral hippocampus) significantly improved performance in the lesioned rats. Atropine (5 mg/kg intraperitoneally or 10 micrograms intraventricularly), but not mecamylamine (3 mg/kg intraperitoneally or 20 micrograms intraventricularly), blocked this action of acetylcholine, suggesting involvement of a muscarinic receptor. Galanin (100-500 ng intraventricularly or 200 ng into the ventral hippocampus) attenuated the ability of acetylcholine to reverse the deficit in working memory in the lesioned rats. The antagonistic interaction between galanin and acetylcholine suggests that endogenous galanin may inhibit cholinergic function in memory processes, particularly in pathologies such as Alzheimer disease that involve degeneration of basal forebrain neurons.

A specific role for septohippocampal acetylcholine in memory?

PubMed Central

Easton, Alexander; Douchamps, Vincent; Eacott, Madeline; Lever, Colin

2012-01-01

Acetylcholine has long been implicated in memory, including hippocampal-dependent memory, but the specific role for this neurotransmitter is difficult to identify in human neuropsychology. Here, we review the evidence for a mechanistic model of acetylcholine function within the hippocampus and consider its explanatory power for interpreting effects resulting from both pharmacological anticholinergic manipulations and lesions of the cholinergic input to the hippocampus in animals. We argue that these effects indicate that acetylcholine is necessary for some, but not all, hippocampal-dependent processes. We review recent evidence from lesion, pharmacological and electrophysiological studies to support the view that a primary function of septohippocampal acetylcholine is to reduce interference in the learning process by adaptively timing and separating encoding and retrieval processes. We reinterpret cholinergic-lesion based deficits according to this view and propose that acetylcholine reduces the interference elicited by the movement of salient locations between events. PMID:22884957

Pressure reversal of the action of octanol on postsynaptic membranes from Torpedo.

PubMed Central

Braswell, L. M.; Miller, K. W.; Sauter, J. F.

1984-01-01

Octanol increases the binding of [3H]-acetylcholine to the desensitized state of the nicotinic receptor in postsynaptic membranes prepared from Torpedo californica. This increase in binding results from an increase in the affinity of [3H]-acetylcholine for its receptor without any change in the number of sites or the shape of the acetylcholine binding curve. High pressures of helium (300 atm) decrease [3H]-acetylcholine binding by a mechanism that changes only the affinity of acetylcholine binding. Helium pressure reverses the effect of octanol on the affinity of [3H]-acetylcholine for its receptor. This pressure reversal of the action of octanol at a postsynaptic membrane is consistent either with pressure counteracting an octanol-induced membrane expansion or with independent mechanisms for the actions of octanol and pressure. The data do not conform with a mechanism in which pressure displaces octanol from a binding site on the receptor protein. PMID:6487895

Asthma-like symptoms, atopy, and bronchial responsiveness in furniture workers

PubMed Central

Talini, D.; Monteverdi, A.; Benvenuti, A.; Petrozzino, M.; Di, P; Lemmi, M.; Carletti, A.; Macchioni, P.; Serretti, N.; Viegi, G.; Paggiaro, P.

1998-01-01

OBJECTIVES: To study the role of individual and occupational risk factors for asthma in furniture workers. METHODS: 296 workers were examined (258 men, 38 women) with a questionnaire of respiratory symptoms and diseases, baseline spirometry, bronchial provocative test with methacholine, and skin prick tests. Non-specific bronchial hyperreactivity was defined as when a provocative dose with a fall of 20% in forced expiratory volume in 1 second (PD20FEV1) was < 0.8 mg and atopy in the presence of at least one positive response to skin prick tests. Workers were subdivided into spray painters (exposed to low concentrations of diisocyanates and solvents), woodworkers (exposed to wood dusts), and assemblers (control group). RESULTS: The prevalences of attacks of shortness of breath with wheezing and dyspnoea were higher in spray painters (13.5% and 11.5% respectively) than in woodworkers (7.7% and 6.3%) or in assemblers (1.6% and 1.6%); prevalences of chronic cough, asthma, and rhinitis were also slightly but not significantly higher in spray painters and in woodworkers than in assemblers. The difference in the prevalence of respiratory symptoms among the job titles was due to the atopic subjects, who showed a higher prevalence of chronic cough, wheeze, shortness of breath with wheeze, dyspnoea, and asthma in spray painters than in the other groups. The prevalence of non-specific bronchial hyperreactivity in subjects who performed bronchial provocative tests was 17.7%, with no significant difference among groups. Asthma symptoms were significantly associated with non-specific bronchial hyperreactivity. Asthma-like symptoms plus non-specific bronchial hyperreactivity was found in 4% of assemblers, 10% of woodworkers, and 13.3% of spray painters (chi 2 = 2.6, NS). Multiple logistic analysis taking into account individual (smoke, atopy, age) and occupational (job titles) risk factors confirmed that spray painters had higher prevalence of chronic cough than assemblers, and a trend in increasing the prevalence of shortness of breath with wheeze, dyspnoea, and asthma. CONCLUSIONS: Painters in the furniture industry, particularly atopic subjects, are at higher risk of asthma-like symptoms than other job titles. In these workers asthma-like symptoms are more sensitive than non-specific bronchial hyperreactivity in detecting a negative effect of the occupational exposure.   PMID:9924457

VRX-03011, a novel 5-HT4 agonist, enhances memory and hippocampal acetylcholine efflux.

PubMed

Mohler, Eric G; Shacham, Sharon; Noiman, Silvia; Lezoualc'h, Frank; Robert, Sylvain; Gastineau, Monique; Rutkowski, Joseph; Marantz, Yael; Dumuis, Aline; Bockaert, Joel; Gold, Paul E; Ragozzino, Michael E

2007-09-01

Recent evidence suggests that 5-hydroxytryptamine (5-HT)(4) receptor activity enhances cognition and provides neuroprotection. Here we report the effects of VRX-03011, a novel partial 5-HT(4) agonist, that is both potent (K(i) approximately 30 nM) and highly selective (K(i) > 5 microM for all other 5-HT receptors tested). In separate experiments, rats received VRX-03011 (0.1-10 mg/kg i.p.) 30 min prior to spontaneous alternation testing in a no-delay or a 30-s delay condition. VRX-03011 (1, 5 and 10 mg/kg, but not 0.1 mg/kg) significantly enhanced delayed spontaneous alternation performance while none of the doses enhanced performance in the no-delay test. VRX-03011 (1 and 5 mg/kg) concomitantly enhanced hippocampal acetylcholine output and delayed spontaneous alternation scores compared to that of vehicle controls, but had no effect on hippocampal acetylcholine release under a resting condition. Moreover, suboptimal doses of VRX-03011 and the acetylcholinesterase inhibitor galanthamine combined to enhance memory. VRX-03011 also regulated amyloid precursor protein (APP) metabolism by inducing a concentration-dependent increase in the non-amyloidogenic soluble form of APP (sAPPalpha) with an EC(50) approximately 1--10 nM. VRX-03011 had no effect on contractile properties in guinea pig ileum or colon preparations with an EC(50) > 10 microM and did not alter rat intestinal transit at doses up to 10 mg/kg. These findings suggest that VRX-03011 may represent a novel treatment for Alzheimer's disease that reduces cognitive impairments and provides neuroprotection without gastrointestinal side effects.

Mice deficient for striatal Vesicular Acetylcholine Transporter (VAChT) display impaired short-term but normal long-term object recognition memory.

PubMed

Palmer, Daniel; Creighton, Samantha; Prado, Vania F; Prado, Marco A M; Choleris, Elena; Winters, Boyer D

2016-09-15

Substantial evidence implicates Acetylcholine (ACh) in the acquisition of object memories. While most research has focused on the role of the cholinergic basal forebrain and its cortical targets, there are additional cholinergic networks that may contribute to object recognition. The striatum contains an independent cholinergic network comprised of interneurons. In the current study, we investigated the role of this cholinergic signalling in object recognition using mice deficient for Vesicular Acetylcholine Transporter (VAChT) within interneurons of the striatum. We tested whether these striatal VAChT(D2-Cre-flox/flox) mice would display normal short-term (5 or 15min retention delay) and long-term (3h retention delay) object recognition memory. In a home cage object recognition task, male and female VAChT(D2-Cre-flox/flox) mice were impaired selectively with a 15min retention delay. When tested on an object location task, VAChT(D2-Cre-flox/flox) mice displayed intact spatial memory. Finally, when object recognition was tested in a Y-shaped apparatus, designed to minimize the influence of spatial and contextual cues, only females displayed impaired recognition with a 5min retention delay, but when males were challenged with a 15min retention delay, they were also impaired; neither males nor females were impaired with the 3h delay. The pattern of results suggests that striatal cholinergic transmission plays a role in the short-term memory for object features, but not spatial location. Copyright © 2016 Elsevier B.V. All rights reserved.

Adolescents' responses to online peer conflict: How self‐evaluation and ethnicity matter

PubMed Central

Bos, Marieke G.N.; Stevenson, Claire E.

2017-01-01

Abstract For parents, online platforms where their children interact with others often feel like a “black box” in terms of what exactly is happening. In this study, we developed an ecologically valid online computer game in which a (computer‐generated) peer teammate tried to provoke frustration, in order to examine (a) adolescents' responses and (b) how indices of self‐evaluation (i.e., sense of coherence and self‐esteem) and demographic variables (i.e., gender and ethnicity) matter to these responses. Like gender, being a member of a minority or majority group may influence how provocations by peers are interpreted, influencing how one responds. Fifteen‐year‐old Dutch and Moroccan‐Dutch adolescents (N = 167) completed self‐reports and played the online computer game. The game indeed elicited frustration, with increased self‐reported anger. Moreover, expressions of displeasure were much more common during and after provocation than before provocation. Crucially, perceived self‐evaluation mattered; higher levels of sense of coherence but lower levels of self‐esteem (only in Moroccan‐Dutch group) contributed to fewer expressions of displeasure. Gender did not play a moderating role. Our findings provide initial insights into individual differences in adolescents' responses in an online peer‐conflict situation. Highlights We studied Dutch and Moroccan-Dutch adolescents' responses during online peer provocation and how self-evaluation and demographic variables matter.Provocation by the (computer-generated) peer teammate increased expressions of displeasure.More sense of coherence but less self-esteem was associated with fewer expressions of displeasure, but ethnicity moderated the effect with self-esteem. PMID:29780286

Adolescents' responses to online peer conflict: How self-evaluation and ethnicity matter.

PubMed

Novin, Sheida; Bos, Marieke G N; Stevenson, Claire E; Rieffe, Carolien

2018-01-01

For parents, online platforms where their children interact with others often feel like a "black box" in terms of what exactly is happening. In this study, we developed an ecologically valid online computer game in which a (computer-generated) peer teammate tried to provoke frustration, in order to examine (a) adolescents' responses and (b) how indices of self-evaluation (i.e., sense of coherence and self-esteem) and demographic variables (i.e., gender and ethnicity) matter to these responses. Like gender, being a member of a minority or majority group may influence how provocations by peers are interpreted, influencing how one responds. Fifteen-year-old Dutch and Moroccan-Dutch adolescents (N = 167) completed self-reports and played the online computer game. The game indeed elicited frustration, with increased self-reported anger. Moreover, expressions of displeasure were much more common during and after provocation than before provocation. Crucially, perceived self-evaluation mattered; higher levels of sense of coherence but lower levels of self-esteem (only in Moroccan-Dutch group) contributed to fewer expressions of displeasure. Gender did not play a moderating role. Our findings provide initial insights into individual differences in adolescents' responses in an online peer-conflict situation. We studied Dutch and Moroccan-Dutch adolescents' responses during online peer provocation and how self-evaluation and demographic variables matter.Provocation by the (computer-generated) peer teammate increased expressions of displeasure.More sense of coherence but less self-esteem was associated with fewer expressions of displeasure, but ethnicity moderated the effect with self-esteem.

Testosterone causes both prosocial and antisocial status-enhancing behaviors in human males

PubMed Central

Dreher, Jean-Claude; Pazderska, Agnieszka; Frodl, Thomas; Nolan, John J.; O’Doherty, John P.

2016-01-01

Although popular discussion of testosterone’s influence on males often centers on aggression and antisocial behavior, contemporary theorists have proposed that it instead enhances behaviors involved in obtaining and maintaining a high social status. Two central distinguishing but untested predictions of this theory are that testosterone selectively increases status-relevant aggressive behaviors, such as responses to provocation, but that it also promotes nonaggressive behaviors, such as generosity toward others, when they are appropriate for increasing status. Here, we tested these hypotheses in healthy young males by injecting testosterone enanthate or a placebo in a double-blind, between-subjects, randomized design (n = 40). Participants played a version of the Ultimatum Game that was modified so that, having accepted or rejected an offer from the proposer, participants then had the opportunity to punish or reward the proposer at a proportionate cost to themselves. We found that participants treated with testosterone were more likely to punish the proposer and that higher testosterone levels were specifically associated with increased punishment of proposers who made unfair offers, indicating that testosterone indeed potentiates aggressive responses to provocation. Furthermore, when participants administered testosterone received large offers, they were more likely to reward the proposer and also chose rewards of greater magnitude. This increased generosity in the absence of provocation indicates that testosterone can also cause prosocial behaviors that are appropriate for increasing status. These findings are inconsistent with a simple relationship between testosterone and aggression and provide causal evidence for a more complex role for testosterone in driving status-enhancing behaviors in males. PMID:27671627

Intra- and inter-rater reliability of 3D passive intervertebral motion in subjects with nonspecific neck pain assessed by physical therapy students: A pilot study.

PubMed

Rossettini, Giacomo; Rondoni, Angie; Lovato, Tommaso; Strobe, Marco; Verzè, Elisa; Vicentini, Marco; Testa, Marco

2016-06-03

Passive Intervertebral Movements (PIVMs) are commonly used to assess and treat patients with nonspecific neck pain. Only very few studies have investigated 3D movements until now. This study assessed intra- and inter-rater reliability of three-dimensional (3D) cervical PIVMs performed by physical therapy students in patients with nonspecific neck pain. Thirty-one patients, mean age 47.2 ± 7.2 years, were independently evaluated by 2 physical therapy students. The raters (A and B) assessed mobility, end-feel and pain provocation performing bilaterally the 3D cervical segmental side-bending test (3D CSSB) from levels C2-C3 to C6-C7. Percentage agreement (raw, positive and negative), Cohen's kappa (95% CI), prevalence index and bias index were calculated to estimate intra- and inter-reliability. Intra-rater reliability showed kappa values ranging between fair and substantial (k 0.29-0.80) for pain provocation, mobility and end-feel, with percentage agreements between 61%-90%. Inter-rater reliability presented kappa values ranging between fair and substantial (k 0.22-0.62) for pain provocation, mobility and end-feel, with percentage agreements between 61% and 80%. Intra-rater reliability of 3D PIVMs was superior to inter-rater reliability in patients with nonspecific neck pain. The most repeatable evaluation parameter was pain. However overall poor reliability suggests avoiding the use of these techniques alone to examine patients and measure their outcome. Further studies are needed to investigate PIVMs reliability in combination with other assessment procedure in symptomatic patients.

MAOA-uVNTR genotype predicts interindividual differences in experimental aggressiveness as a function of the degree of provocation.

PubMed

Kuepper, Yvonne; Grant, Phillip; Wielpuetz, Catrin; Hennig, Juergen

2013-06-15

The MAOA-uVNTR has been suggested to play a role regarding aggression, however, results are inconsistent. We aimed at further elucidating potential effects of the MAOA-uVNTR on aggressiveness with respect to potential modulators: sex, experimental vs. trait aggressiveness and type of aggressiveness (proactive vs. reactive aggressiveness). We tested 239 healthy young adults (88 men/151 women). Participants were genotyped for the MAOA-uVNTR and performed a modified version of a competitive reaction time task - a commonly used and well established tool to elicit and measure aggressiveness. Furthermore, they completed a self-report scale measuring trait aggressiveness. We found a main effect of MAOA-uVNTR on a measure of reactive aggressiveness for both men and women, whereby the low-activity alleles of the MAOA-uVNTR were associated with substantially increased aggressive reactions (p<.05). This effect was unique for reactive aggressiveness. Measures of proactive aggressiveness or self reports were not associated with the MAOA-uVNTR-genotype. Our data are in line with earlier studies and indicate the MAOA-uVNTR-genotype to be specifically associated with measures of reactive impulsive experimental aggressiveness in healthy men and women. Furthermore the association between the MAOA-uVNTR genotype and aggressive responses increases in a fashion linear to the degree of provocation. This indicates that the low-functional alleles of the MAOA-uVNTR are not associated with increased aggressive behavior per se, but rather with an increased aggressive reactivity to provocation. Copyright © 2013 Elsevier B.V. All rights reserved.

Epithelial propionyl‐ and butyrylcholine as novel regulators of colonic ion transport

PubMed Central

Moreno, Sarah; Gerbig, Stefanie; Schulz, Sabine; Spengler, Bernhard; Bader, Sandra

2016-01-01

Abstract Background and Purpose The colonic surface epithelium produces acetylcholine, released after the binding of propionate to GPCRs for this short‐chain fatty acid (SCFA). This epithelial acetylcholine then induces anion secretion via stimulation of acetylcholine receptors. The key enzyme responsible for acetylcholine synthesis, choline acetyltransferase, is known to be unselective as regards the fatty acid used for esterification of choline. As the colonic epithelium is permanently exposed to high concentrations of different SCFAs produced by bacterial fermentation, we investigated whether choline esters other than acetylcholine, propionylcholine and butyrylcholine, are produced by the colonic epithelium, too, and whether these ‘atypical’ esters are able to stimulate the acetylcholine receptors involved in the regulation of colonic ion transport. Experimental Approach Desorption electrospray ionization mass spectroscopy (DESI‐MS), Ussing chamber and Ca2+‐imaging experiments were performed on rat distal colon. Key Results DESI‐MS analyses revealed the production of acetylcholine, propionylcholine and butyrylcholine in the surface epithelium. Relative expression rates were 2–3% in comparison with acetylcholine. In Ussing chamber experiments, both atypical choline esters caused a concentration‐dependent increase in short‐circuit current, that is, stimulated anion secretion. Inhibitor experiments in the absence and presence of the submucosal plexus revealed the involvement of neuronal and epithelial acetylcholine receptors. While butyrylcholine obviously stimulated both nicotinic and muscarinic receptors, propionylcholine predominantly acted on muscarinic receptors. Conclusions and Implications These results suggest a novel pathway for communication between intestinal microbes producing SCFA and the host via modification of epithelial production of choline esters involved in the paracrine regulation of the colonic epithelium. PMID:27423041

B-973, a novel piperazine positive allosteric modulator of the α7 nicotinic acetylcholine receptor.

PubMed

Post-Munson, Debra J; Pieschl, Rick L; Molski, Thaddeus F; Graef, John D; Hendricson, Adam W; Knox, Ronald J; McDonald, Ivar M; Olson, Richard E; Macor, John E; Weed, Michael R; Bristow, Linda J; Kiss, Laszlo; Ahlijanian, Michael K; Herrington, James

2017-03-15

The alpha7 (α7) nicotinic acetylcholine receptor is a therapeutic target for cognitive disorders. Here we describe 3-(3,4-difluorophenyl)-N-(1-(6-(4-(pyridin-2-yl)piperazin-1-yl)pyrazin-2-yl)ethyl)propanamide (B-973), a novel piperazine-containing molecule that acts as a positive allosteric modulator of the α7 receptor. We characterize the action of B-973 on the α7 receptor using electrophysiology and radioligand binding. At 0.1mM acetylcholine, 1μM B-973 potentiated peak acetylcholine-induced currents 6-fold relative to maximal acetylcholine (3mM) and slowed channel desensitization, resulting in a 6900-fold increase in charge transfer. The EC 50 of B-973 was approximately 0.3μM at acetylcholine concentrations ranging from 0.03 to 3mM. At a concentration of 1μM, B-973 shifted the acetylcholine EC 50 of peak currents from 0.30mM in control to 0.007mM. B-973 slowed channel deactivation upon acetylcholine removal (τ=50s) and increased the affinity of the α7 agonist [ 3 H]A-585539. In the absence of exogenously added acetylcholine, application of B-973 at concentrations >1μM induced large methyllycaconitine-sensitive currents, suggesting B-973 can function as an Ago-PAM at high concentrations. B-973 will be a useful probe for investigating the biological consequences of increasing α7 receptor activity through allosteric modulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Seeing the World through Mortal Kombat-Colored Glasses: Violent Video Games and the Development of a Short-Term Hostile Attribution Bias.

ERIC Educational Resources Information Center

Kirsh, Steven J.

1998-01-01

Investigated the effects of playing violent versus non-violent video games on the interpretation of ambiguous provocation situation. Found that children playing a violent video game responded more negatively to three of six ambiguous provocation story questions than children playing the non-violent video game. Data suggest that playing violent…

Brain responses to symptom provocation and trauma-related short-term memory recall in coal mining accident survivors with acute severe PTSD.

PubMed

Hou, Cailan; Liu, Jun; Wang, Kun; Li, Lingjiang; Liang, Meng; He, Zhong; Liu, Yong; Zhang, Yan; Li, Weihui; Jiang, Tianzi

2007-05-04

Functional neuroimaging studies have largely been performed in patients with longstanding chronic posttraumatic stress disorder (PTSD). Additionally, memory function of PTSD patients has been proved to be impaired. We sought to characterize the brain responses of patients with acute PTSD and implemented a trauma-related short-term memory recall paradigm. Individuals with acute severe PTSD (n=10) resulting from a mining accident and 7 men exposed to the mining accident without PTSD underwent functional magnetic resonance imaging (fMRI) while performing the symptom provocation and trauma-related short-term memory recall paradigms. During symptom provocation paradigm, PTSD subjects showed diminished responses in right anterior cingulate gyrus, left inferior frontal gyrus and bilateral middle frontal gyrus and enhanced left parahippocampal gyrus response compared with controls. During the short-term memory recall paradigm, PTSD group showed diminished responses in right inferior frontal gyrus, right middle frontal and left middle occipital gyrus in comparison with controls. PTSD group exhibited diminished right parahippocampal gyrus response during the memory recall task as compared to the symptom provocation task. Our findings suggest that neurophysiological alterations and memory performance deficit have developed in acute severe PTSD.

P3 and provoked aggressive behavior.

PubMed

Fanning, Jennifer R; Berman, Mitchell E; Long, James M

2014-01-01

Cognitive and biological processes play a role in human aggression. However, relatively little is known about the neural correlates of cognitive processes in aggressive individuals, particularly as they unfold during an aggressive encounter. We investigated whether the P3 event-related potential (ERP) discriminates aggressive versus nonaggressive individuals during a provocative, aggressive encounter. Forty-eight participants (23 men and 25 women) were classified as aggressive or nonaggressive based on self-reported life history of aggression. Aggressive behavior was assessed using a modification of a well-validated laboratory task during which the participant and a fictitious opponent ostensibly delivered and received noise blasts of low, medium, and high intensity. Provocation was manipulated by altering the level of noise set by the opponent. Aggression was defined as the number of high-intensity noise blasts the participant set for the opponent. As predicted, P3 amplitude in response to provocation differed as a function of aggressive history. Nonaggressive individuals showed enhanced P3 when provoked by the opponent relative to low provocation, but this effect was absent in aggressive individuals. The results suggest that aggressive individuals engage fewer neural processing resources in response to provoking social cues, which may reflect aberrant cognitive and emotional processes.

Critically appraised topic on adverse food reactions of companion animals (4): can we diagnose adverse food reactions in dogs and cats with in vivo or in vitro tests?

PubMed

Mueller, Ralf S; Olivry, Thierry

2017-08-30

The gold standard to diagnose adverse food reactions (AFRs) in the dog and cat is currently an elimination diet with subsequent provocation trials. However, those trials are inconvenient and client compliance can be low. Our objective was to systematically review the literature to evaluate in vivo and in vitro tests used to diagnose AFR in small animals. We searched three databases (CAB Abstracts, MEDLINE and Web of Science) for pertinent references on September 16, 2016. Among 71, 544 and 41 articles found in the CAB Abstract, MEDLINE and Web of Science databases, respectively, we selected 22 articles and abstracts from conference proceedings that reported data usable for evaluation of tests for AFR. Serum tests for food-specific IgE and IgG, intradermal testing with food antigens, lymphocyte proliferation tests, fecal food-specific IgE, patch, gastroscopic, and colonoscopic testing were evaluated. Testing for serum food-specific IgE and IgG showed low repeatability and, in dogs, a highly variable accuracy. In cats, the accuracy of testing for food-specific IgE was low. Lymphocyte proliferation tests were more frequently positive and more accurate in animals with AFR, but, as they are more difficult to perform, they remain currently a research tool. All other reported tests were only evaluated by individual studies with small numbers of animals. Negative patch test reactions have a very high negative predictability in dogs and could enable a choice of ingredients for the elimination diet in selected patients. Gastroscopic and colonoscopic testing as well as food-specific fecal IgE or food-specific serum IgG measurements appear less useful. Currently, the best diagnostic procedure to identify AFRs in small animals remains an elimination diet with subsequent provocation trials.

Specific stimulated uptake of acetylcholine by Torpedo electric organ synaptic vesicles.

PubMed Central

Parsons, S M; Koenigsberger, R

1980-01-01

The specificity of acetylcholine uptake by synaptic vesicles isolated from the electric organ of Torpedo californica was studied. In the absence of cofactors, [3H]acetylcholine was taken up identically to[14C]choline in the same solution (passive uptake), and the equilibrium concentration achieved inside the vesicles was equal to the concentration outside. In the presence of MgATP, [3H]acetylcholine and [14C]choline in the same solution were taken up identically, except only about half as much of each was taken up (suppressed uptake). [3H]Acetylcholine uptake was stimulated by MgATP and HCO3- about 4-fold relative to suppressed uptake, for a net concentrative uptake of about 2:1 (stimulated uptake). Uptake of [14C]choline in the same solution remained at the suppressed level. [3H]Acetylcholine taken up under stimulated conditions migrated with vesicles containing [14C]mannitol on analytical glycerol density gradients during centrifugation. Vesicle were treated with nine protein modification reagents under mild conditions. Two reagents had no effect on, dithiothreitol potentiated, and six reagents strongly inhibited subsequent stimulated uptake of [3H]acetylcholine. The results indicate that uptake of acetylcholine is conditionally specific for the transported substrate, is carried out by the synaptic vesicles rather than a contaminant of the preparation, and requires a functional protein system containing a critical sulfhydryl group. PMID:6934549

Lipid Emulsion Attenuates Acetylcholine-Induced Relaxation in Isolated Rat Aorta

PubMed Central

Ok, Seong-Ho; Lee, Soo Hee; Yu, Jongsun; Park, Jungchul; Shin, Il-Woo; Lee, Youngju; Cho, Hyunhoo; Choi, Mun-Jeoung; Baik, Jiseok; Hong, Jeong-Min; Han, Jeong Yeol; Lee, Heon Keun; Chung, Young-Kyun; Sohn, Ju-Tae

2015-01-01

We investigated the effect of Lipofundin MCT/LCT and Intralipid on acetylcholine-induced nitric oxide- (NO-) mediated relaxation in rat aorta to determine which lipid emulsion (LE) is more potent in terms of inhibition of NO-induced relaxation. Dose-response curves of responses induced by acetylcholine, the calcium ionophore A23187, and sodium nitroprusside were generated using isolated rat aorta with or without LE. The effect of Lipofundin MCT/LCT on acetylcholine-induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells (HUVECs) was investigated using western blotting. Lipofundin MCT/LCT (0.1 and 0.2%) attenuated acetylcholine-induced relaxation in endothelium-intact aorta with or without tiron, whereas 0.2% Intralipid only inhibited relaxation. Lipofundin MCT/LCT inhibited relaxation induced by the calcium ionophore A23187 and sodium nitroprusside in endothelium-intact aorta, but Lipofundin MCT/LCT had no effect on sodium nitroprusside-induced relaxation in the endothelium-denuded aorta. Combined pretreatment with l-arginine plus Lipofundin MCT/LCT increased acetylcholine-induced maximal relaxation in endothelium-intact aorta compared with Lipofundin MCT/LCT alone. l-Arginine attenuated Lipofundin MCT/LCT-mediated inhibition of acetylcholine-induced eNOS phosphorylation in HUVECs. Taken together, Lipofundin MCT/LCT attenuated acetylcholine-induced NO-mediated relaxation via an inhibitory effect on the endothelium including eNOS, which is proximal to activation of guanylyl cyclase. PMID:26273653

Lipid Emulsion Attenuates Acetylcholine-Induced Relaxation in Isolated Rat Aorta.

PubMed

Ok, Seong-Ho; Lee, Soo Hee; Yu, Jongsun; Park, Jungchul; Shin, Il-Woo; Lee, Youngju; Cho, Hyunhoo; Choi, Mun-Jeoung; Baik, Jiseok; Hong, Jeong-Min; Han, Jeong Yeol; Lee, Heon Keun; Chung, Young-Kyun; Sohn, Ju-Tae

2015-01-01

We investigated the effect of Lipofundin MCT/LCT and Intralipid on acetylcholine-induced nitric oxide- (NO-) mediated relaxation in rat aorta to determine which lipid emulsion (LE) is more potent in terms of inhibition of NO-induced relaxation. Dose-response curves of responses induced by acetylcholine, the calcium ionophore A23187, and sodium nitroprusside were generated using isolated rat aorta with or without LE. The effect of Lipofundin MCT/LCT on acetylcholine-induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells (HUVECs) was investigated using western blotting. Lipofundin MCT/LCT (0.1 and 0.2%) attenuated acetylcholine-induced relaxation in endothelium-intact aorta with or without tiron, whereas 0.2% Intralipid only inhibited relaxation. Lipofundin MCT/LCT inhibited relaxation induced by the calcium ionophore A23187 and sodium nitroprusside in endothelium-intact aorta, but Lipofundin MCT/LCT had no effect on sodium nitroprusside-induced relaxation in the endothelium-denuded aorta. Combined pretreatment with l-arginine plus Lipofundin MCT/LCT increased acetylcholine-induced maximal relaxation in endothelium-intact aorta compared with Lipofundin MCT/LCT alone. L-Arginine attenuated Lipofundin MCT/LCT-mediated inhibition of acetylcholine-induced eNOS phosphorylation in HUVECs. Taken together, Lipofundin MCT/LCT attenuated acetylcholine-induced NO-mediated relaxation via an inhibitory effect on the endothelium including eNOS, which is proximal to activation of guanylyl cyclase.

On the Rebound: The Alliance Faces New Tests

DTIC Science & Technology

2012-06-01

alliance. After several tumultuous years, the two countries regained their footing when responding to the March 11 triple catastrophe, moving forward...Japan after March 11. In the aftermath of the triple tragedy, some believed that the scale of the disaster would force change on Japan. The...provocations. If correct, this analysis has profound implications for bilateral relations, because it means that key to extended deterrence after the Nuclear

Cutaneous adverse reactions to amoxicillin-clavulanic acid suspension in children: the role of sodium benzoate.

PubMed

Mori, Francesca; Barni, Simona; Pucci, Neri; Rossi, Maria Elisabetta; de Martino, Maurizio; Novembre, Elio

2012-04-01

In Europe amoxicillin plus clavulanic acid is the most commonly prescribed antibiotic and sodium benzoate is contained in the suspension formulation as a preservative. We studied the relevance of sodium benzoate as the culprit agent. In a group of children with a history of adverse reactions to amoxicillin plus clavulanic acid suspension. A total of 89 children were enrolled over a period of 3 years (2006 - 2009). Single blind oral provocation tests (OPTs) with amoxicillin plus clavulanic acid, sodium benzoate and placebo were performed. 20 children with recurrent idiopathic urticaria were investigated as a control group. according to personal history: 70% of reactions were late in developing while 23% of reactions were immediate and for 5% of the cases it was not possible to define the timing. 8 children (8/89=9%) resulted positive to the provocation tests with amoxicillin plus clavulanic acid; ten children (10/89=11%) had positive results with sodium benzoate; 3% had a double positivity (i.e. excipient and active drug). The timing of reactions significantly differs between the Amoxicillin plus clavulanic acid and sodium benzoate groups (p=0.002). Sodium benzoate probably acts through a non-immunologic mechanism and care should be given to children allergic to sodium benzoate containing pharmaceutical formulations.

Influence of headache frequency on clinical signs and symptoms of TMD in subjects with temple headache and TMD pain

PubMed Central

Anderson, Gary C.; John, Mike T.; Ohrbach, Richard; Nixdorf, Donald R.; Schiffman, Eric L.; Truelove, Edmond S.; List, Thomas

2011-01-01

The relationship of the frequency of temple headache to signs and symptoms of temporomandibular disorders (TMD) was investigated in a subset of a larger convenience sample of community TMD cases. The study sample included: 86 painful TMD, non-headache subjects; 309 painful TMD subjects with varied frequency of temple headaches; and 149 subjects without painful TMD or headache for descriptive comparison. Painful TMD included Research Diagnostic Criteria (RDC) diagnoses of myofascial pain, TMJ arthralgia and TMJ osteoarthritis. Mild to moderate intensity temple headaches were classified by frequency using criteria based on the ICHD-II classification of TTH. Outcomes included TMD signs and symptoms (pain duration, pain intensity, number of painful masticatory sites on palpation, mandibular range of motion), PPTs and temple headache resulting from masticatory provocation tests. Trend analyses across the painful TMD groups showed a substantial trend for aggravation of all of the TMD signs and symptoms associated with increased frequency of the temple headaches. In addition, increased headache frequency showed significant trends associated with reduced PPTs and reported temple headache with masticatory provocation tests. In conclusion, these findings suggest that these headaches may be TMD-related, as well as a possible role for peripheral and central sensitization in TMD patients. PMID:21196079

Assaultive behavior. Does provocation begin in the front office?

PubMed

Blair, D T

1991-05-01

1. Provocation is an important risk predictor because these issues can be recognized, assessed, and appropriate interventions can be implemented to reduce the associated risks. It is only by the reduction of such "non-fixed" risk factors that any reduction of assaults can be accomplished. 2. Involuntary admission, patients with dementia or organic brain disorder, physical or verbal limits, staff attitude, denial of the possibility of assaults, and the educational level and clinical experience of the staff may help provoke an assaultive episode. 3. An important step is assessing the assault to identify provocation due to certain medical causes, and to document the extent of degeneration in patients with dementia or organic brain disorder. Medical intervention would be indicated and would appropriately address the causes of some violent episodes.

Sub-anesthetic concentrations of (R,S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors

PubMed Central

Moaddel, Ruin; Abdrakhmanova, Galia; Kozak, Joanna; Jozwiak, Krzysztof; Toll, Lawrence; Jimenez, Lucita; Rosenberg, Avraham; Tran, Thao; Xiao, Yingxian; Zarate, Carlos A.; Wainer, Irving W.

2012-01-01

The effect of the (R,S)-ketamine metabolites (R,S)-norketamine, (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)- hydroxynorketamine on the activity of α7 and α3β4 neuronal nicotinic acetylcholine receptors was investigated using patch-clamp techniques. The data indicated that (R,S)-dehydronorketamine inhibited acetylcholine-evoked currents in α7-nicotinic acetylcholine receptor, IC50 = 55 ± 6 nM, and that (2S,6S)-hydroxynorketamine, (2R,6R)-hydroxynorketamine and (R,S)-norketamine also inhibited α7-nicotinic acetylcholine receptor function at concentrations ≤1μM, while (R,S)-ketamine was inactive at these concentrations. The inhibitory effect of (R,S)-dehydronorketamine was voltage-independent and the compound did not competitively displace selective α7-nicotinic acetylcholine receptor ligands [125I]-α-bungarotoxin and [3H]-epibatidine indicating that (R,S)-dehydronorketamine is a negative allosteric modulator of the α7-nicotinic acetylcholine receptor. (R,S)-Ketamine and (R,S)-norketamine inhibited (S)-nicotine-induced whole-cell currents in cells expressing α3β4-nicotinic acetylcholine receptor, IC50 3.1 and 9.1μM, respectively, while (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine were weak inhibitors, IC50 >100μM. The binding affinities of (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine at the NMDA receptor were also determined using rat brain membranes and the selective NMDA receptor antagonist [3H]-MK-801. The calculated Ki values were 38.95 μM for (S)-dehydronorketamine, 21.19 μM for (2S,6S)-hydroxynorketamine and > 100 μM for (2R,6R)-hydroxynorketamine. The results suggest that the inhibitory activity of ketamine metabolites at the α7-nicotinic acetylcholine receptor may contribute to the clinical effect of the drug. PMID:23183107

The prevalence of tarsal tunnel syndrome in patients with lumbosacral radiculopathy.

PubMed

Zheng, Chaojun; Zhu, Yu; Jiang, Jianyuan; Ma, Xiaosheng; Lu, Feizhou; Jin, Xiang; Weber, Robert

2016-03-01

Tarsal tunnel syndrome (TTS) is a painful foot condition. Lumbosacral radiculopathy (LR) may also present with symptoms occurring in TTS. However, no studies have been reported to determine the possible coexistence of these two conditions. The aim of our study was to identify the prevalence of TTS in patients with confirmed LR and to analyze the clinical and electrodiagnostic features of patients with both TTS and LR. Medial and lateral plantar nerve mixed studies, peroneal motor studies and deep peroneal sensory studies were performed in 81 normal subjects and 561 patients with LR. The Tinel's test and other provocative tests were performed in the LR patient group, and the clinical symptoms of TTS were also analyzed. The frequency of TTS was investigated in all radiculopathy group patients with different nerve root lesions. Concomitant TTS was found in 27 (4.8%) patients with LR. Abnormal results of sensory/mixed conduction tests were observed in 25/27 (92.6%) patients, and 11/27 (40.7%) patients had abnormal results of motor conduction tests. Positivity for the Tinel's test and special provocative tests was found in 15/27 (55.6%) and 17/27 (63.0%) patients, respectively. Overall, 9/27 (33.3%) patients had typical symptoms, and suspicious clinical symptoms were found in the other 14/27 (51.9%) patients. The frequency of coexisting TTS was not statistically different among the single-level L4, L5 or S1 radiculopathy, or between the single-level and multi-level radiculopathies (P > 0.05). The findings suggest that the prevalence of TTS is significant in patients with LR. Thus, more caution should be paid when diagnosing and managing patients with LR due to the possible existence of TTS, as their management strategies are quite different.

A selective molecularly imprinted polymer for immobilization of acetylcholinesterase (AChE): an active enzyme targeted and efficient method.

PubMed

Demirci, Gökhan; Doğaç, Yasemin İspirli; Teke, Mustafa

2015-11-01

In the present study, we immobilized acetylcholinesterase (AChE) enzyme onto acetylcholine removed imprinted polymer and acetylcholine containing polymer. First, the polymers were produced with acetylcholine, substrate of AChE, by dispersion polymerization. Then, the enzyme was immobilized onto the polymers by using two different methods: In the first method (method A), acetylcholine was removed from the polymer, and then AChE was immobilized onto this polymer (acetylcholine removed imprinted polymer). In the second method (method B), AChE was immobilized onto acetylcholine containing polymer by affinity. In method A, enzyme-specific species (binding sites) occurred by removing acetylcholine from the polymer. The immobilized AChE reached 240% relative specific activity comparison with free AChE because the active enzyme molecules bounded onto the polymer. Transmission electron microscopy results were taken before and after immobilization of AChE for the assessment of morphological structure of polymer. Also, the experiments, which include optimum temperature (25-65 °C), optimum pH (3-10), thermal stability (4-70 °C), kinetic parameters, operational stability and reusability, were performed to determine the characteristic of the immobilized AChE. Copyright © 2015 John Wiley & Sons, Ltd.

Dimethylaminoethanol (deanol) metabolism in rat brain and its effect on acetylcholine synthesis.

PubMed

Jope, R S; Jenden, D J

1979-12-01

Specific methods utilizing combined gas chromatography mass spectrometry were used to measure the metabolism of [2H6] deanol and its effects on acetylcholine concentration in vitro and in vivo. In vitro [2H6]deanol was rapidly taken up by rat brain synaptosomes, but was neither methylated nor acetylated. [2H6]Deanol was a weak competitive inhibitor of the high affinity transport of [2H4]choline, thus reducing the synthesis of [2H4]acetylcholine. In vivo [2H6]deanol was present in the brain after i.p. or p.o. administration, but was not methylated or acetylated. Treatment of rats with [2H6]deanol significantly increased the concentration of choline in the plasma and brain but did not alter the concentration of acetylcholine in the brain. Treatment of rats with atropine (to stimulate acetylcholine turnover) or with hemicholinium-3 (to inhibit the high affinity transport of choline) did not reveal any effect of [2H6]deanol on acetylcholine synthesis in vivo. However, since [2H6]deanol did increase brain choline, it may prove therapeutically useful when the production of choline is reduced or when the utilization of choline for the synthesis of acetylcholine is impaired.

Endogenous acetylcholine increases alveolar epithelial fluid transport via activation of alveolar epithelial Na,K-ATPase in mice.

PubMed

Li, Xia; Yan, Xi Xin; Li, Hong Lin; Li, Rong Qin

2015-10-01

The contribution of endogenous acetylcholine to alveolar fluid clearance (AFC) and related molecular mechanisms were explored. AFC was measured in Balb/c mice after vagotomy and vagus nerve stimulation. Effects of acetylcholine chloride on AFC in Kunming mice and Na,K-ATPase function in A549 alveolar epithelial cells also were determined. AFC significantly decreased in mice with left cervical vagus nerve transection compared with controls (48.69 ± 2.57 vs. 66.88 ± 2.64, P ≤ 0.01), which was reversed by stimulation of the peripheral (60.81 ± 1.96, P ≤ 0.01). Compared with control, acetylcholine chloride dose-dependently increased AFC and elevated Na,K-ATPase activity, and these increases were blocked or reversed by atropine. These effects were accompanied by recruitment of Na,K-ATPase α1 to the cell membrane. Thus, vagus nerves participate in alveolar epithelial fluid transport by releasing endogenous acetylcholine in the infusion-induced pulmonary edema mouse model. Effects of endogenous acetylcholine on AFC are likely mediated by Na,K-ATPase function through activation of muscarinic acetylcholine receptors on alveolar epithelia. Copyright © 2015 Elsevier B.V. All rights reserved.

Subunit profiling and functional characteristics of acetylcholine receptors in GT1-7 cells.

PubMed

Arai, Yuki; Ishii, Hirotaka; Kobayashi, Makito; Ozawa, Hitoshi

2017-03-01

GnRH neurons form a final common pathway for the central regulation of reproduction. Although the involvement of acetylcholine in GnRH secretion has been reported, direct effects of acetylcholine and expression profiles of acetylcholine receptors (AChRs) still remain to be studied. Using immortalized GnRH neurons (GT1-7 cells), we analyzed molecular expression and functionality of AChRs. Expression of the mRNAs were identified in the order α7 > β2 = β1 ≧ α4 ≧ α5 = β4 = δ > α3 for nicotinic acetylcholine receptor (nAChR) subunits and m4 > m2 for muscarinic acetylcholine receptor (mAChR) subtypes. Furthermore, this study revealed that α7 nAChRs contributed to Ca 2+ influx and GnRH release and that m2 and m4 mAChRs inhibited forskolin-induced cAMP production and isobutylmethylxanthine-induced GnRH secretion. These findings demonstrate the molecular profiles of AChRs, which directly contribute to GnRH secretion in GT1-7 cells, and provide one possible regulatory action of acetylcholine in GnRH neurons.

Electrophysiological and mechanical effects of substance P and acetylcholine on rabbit aorta.

PubMed Central

Bény, J L; Brunet, P C

1988-01-01

1. The mechanical and electrical properties of smooth muscle cells of the rabbit aorta were recorded simultaneously using respectively a force transducer and a 3 M-KCl-filled glass microelectrode. 2. Acetylcholine had two effects depending on concentration. At low concentration, it caused a persistent endothelium-dependent relaxation and hyperpolarization. At higher concentrations the acetylcholine endothelium-dependent relaxation summed with an endothelium-independent contraction. 3. Substance P caused a transient endothelium-dependent relaxation and hyperpolarization. 4. Acetylcholine and substance P depolarized and contracted de-endothelialized smooth muscle. When the de-endothelialized strip was pre-contracted by noradrenaline, acetylcholine depolarized the muscle but substance P did not. 5. In a 'cascade' experiment, the perfusate from an upstream intact aorta passed over a downstream de-endothelialized strip. Acetylcholine and substance P relaxed the downstream strip showing that they released an endothelial humoral factor which relaxes smooth muscle. 6. The results suggest a constant release of a factor from the endothelial cells which hyperpolarizes the smooth muscle cells in the media. Activation of acetylcholine and substance P receptors on the endothelium accelerates the release of this factor and causes vasodilatation. PMID:2455799

The effects of atropine and oxotremorine on acetylcholine release in rat phrenic nerve-diaphragm preparations.

PubMed Central

Abbs, E. T.; Joseph, D. N.

1981-01-01

1 Atropine (10(-5) M) enhanced the release of [3H]-acetylcholine from rat isolated hemidiaphragms, previously incubated with [3H-methyl]-choline, stimulated via their phrenic nerves. 2 Oxotremorine (10(-5) M) did not affect the stimulated release of [3H]-acetylcholine but antagonized the facilitatory effects of atropine (10(-5) M). 3 It is suggested that there are presynaptic inhibitory muscarinic receptors that modulate the release of acetylcholine in the phrenic nerves of the rat. PMID:7236997

Immuno-detection of OCTN1 (SLC22A4) in HeLa cells and characterization of transport function.

PubMed

Pochini, Lorena; Scalise, Mariafrancesca; Indiveri, Cesare

2015-11-01

OCTN1 was immuno-detected in the cervical cancer cell HeLa, in which the complete pattern of acetylcholine metabolizing enzymes is expressed. Comparison of immuno-staining intensity of HeLa OCTN1 with the purified recombinant human OCTN1 allowed measuring the specific OCTN1 concentration in the HeLa cell extract and, hence calculating the HeLa OCTN1 specific transport activity that was about 10 nmol×min(-1)×mg protein(-1), measured as uptake of [(3)H]acetylcholine in proteoliposomes reconstituted with HeLa extract. This value was very similar to the specific activity of the recombinant protein. Acetylcholine transport was suppressed by incubation of the protein or proteoliposomes with the anti-OCTN1 antibody and was strongly inhibited by PLP and MTSEA, known inhibitors of OCTN1. The absence of ATP in the internal side of proteoliposomes strongly impaired transport function of both the HeLa and, as expected, the recombinant OCTN1. HeLa OCTN1 was inhibited by spermine, NaCl (Na(+)), TEA, γ-butyrobetaine, choline, acetylcarnitine and ipratropium but not by neostigmine. Besides acetylcholine, choline was taken up by HeLa OCTN1 proteoliposomes. The transporter catalyzed also acetylcholine and choline efflux which, differently from uptake, was not inhibited by MTSEA. Time course of [(3)H]acetylcholine uptake in intact HeLa cells was measured. As in proteoliposomes, acetylcholine transport in intact cells was inhibited by TEA and NaCl. Efflux of [(3)H]acetylcholine occurred in intact cells, as well. The experimental data concur in demonstrating a role of OCTN1 in transporting acetylcholine and choline in HeLa cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Fluorescence lifetime spectroscopy: potential for in-vivo estimation of skin fluorophores changes after low power laser treatment

NASA Astrophysics Data System (ADS)

Ferulova, Inesa; Lihachev, Alexey; Spigulis, Janis

2013-11-01

The impact of visible cwlaser irradiation on skin autofluorescence lifetimes was investigated in spectral range from 450 nm to 600 nm. Skin optical provocations were performed during 1 min by 405 nm low power cw laser with power density up to 20 mW/cm2. Autofluorescence lifetimes were measured before and immediately after the optical provocation.

The Relation between Early Adolescents' Trust Beliefs in Peers and Reactions to Peer Provocation: Attributions of Intention and Retaliation

ERIC Educational Resources Information Center

Rotenberg, Ken J.; Betts, Lucy R.; Moore, Jolene

2013-01-01

The authors examined the relation between early adolescents' trust beliefs in peers and both their attributions for, and retaliatory aggression to, peer provocation. One hundred and eight-five early adolescents (102 male) from the United Kingdom (M age = 12 years, 2 months, SD = 3 months) completed the Children's Generalized Trust Beliefs in peer…

ExPPNing how acetylcholine improves gait in Parkinson's disease: An Editorial Highlight for 'Deletion of the Vesicular Acetylcholine Transporter from Pedunculopontine/laterodorsal tegmental neurons modifies gait'.

PubMed

Falkenburger, Björn

2017-03-01

Read the highlighted article 'Deletion of the Vesicular Acetylcholine Transporter from Pedunculopontine/laterodorsal tegmental neurons modifies gait' on page 787. © 2017 International Society for Neurochemistry.

[Intern(euron)al affairs : The role of specific neocortical interneuron classes in the interaction between acetylcholine and GABAergic anesthetics].

PubMed

Liebig, L; Grasshoff, C; Hentschke, H

2016-08-01

Acetylcholine is a neuromodulator which is released throughout the central nervous system and plays an essential role in consciousness and cognitive processes including attention and learning. Due to its 'activating' effect on the neuronal and behavioral level its interaction with anesthetics has long been of interest to anesthesiologists. It is widely held that a reduction of the release of acetylcholine by general anesthetics constitutes part of the anesthetic effect. This notion is backed by numerous human and animal studies, but is also in seeming contradiction to findings that acetylcholine activates specific classes of inhibitory neurons: if acetylcholine excites elements within the neuronal network responsible for the release of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), its withdrawal should diminish, not enhance, the effect of anesthetics.Focusing on cortical circuits, we present an overview of recent advances in cellular neurophysiology, particularly the interactions between inhibitory neuron classes, which provide insights on the interaction between acetylcholine and GABA.

Central nervous system promotes thermotolerance via FoxO/DAF-16 activation through octopamine and acetylcholine signaling in Caenorhabditis elegans.

PubMed

Furuhashi, Tsubasa; Sakamoto, Kazuichi

2016-03-25

The autonomic nervous system (ANS) responds to many kinds of stressors to maintain homeostasis. Although the ANS is believed to regulate stress tolerance, the exact mechanism underlying this is not well understood. To understand this, we focused on longevity genes, which have functions such as lifespan extension and promotion of stress tolerance. To understand the relationship between ANS and longevity genes, we analyzed stress tolerance of Caenorhabditis elegans treated with octopamine, which has an affinity to noradrenaline in insects, and acetylcholine. Octopamine and acetylcholine did not show resistance against H2O2, but the neurotransmitters promoted thermotolerance via DAF-16. However, chronic treatment with octopamine and acetylcholine did not extend the lifespan, although DAF-16 plays an important role in longevity. In conclusion, our results show that octopamine and acetylcholine activate DAF-16 in response to stress, but chronic induction of octopamine and acetylcholine is not beneficial for increasing longevity. Copyright © 2016 Elsevier Inc. All rights reserved.

Coordinated Acetylcholine Release in Prefrontal Cortex and Hippocampus Is Associated with Arousal and Reward on Distinct Timescales.

PubMed

Teles-Grilo Ruivo, Leonor M; Baker, Keeley L; Conway, Michael W; Kinsley, Peter J; Gilmour, Gary; Phillips, Keith G; Isaac, John T R; Lowry, John P; Mellor, Jack R

2017-01-24

Cholinergic neurotransmission throughout the neocortex and hippocampus regulates arousal, learning, and attention. However, owing to the poorly characterized timing and location of acetylcholine release, its detailed behavioral functions remain unclear. Using electrochemical biosensors chronically implanted in mice, we made continuous measurements of the spatiotemporal dynamics of acetylcholine release across multiple behavioral states. We found that tonic levels of acetylcholine release were coordinated between the prefrontal cortex and hippocampus and maximal during training on a rewarded working memory task. Tonic release also increased during REM sleep but was contingent on subsequent wakefulness. In contrast, coordinated phasic acetylcholine release occurred only during the memory task and was strongly localized to reward delivery areas without being contingent on trial outcome. These results show that coordinated acetylcholine release between the prefrontal cortex and hippocampus is associated with reward and arousal on distinct timescales, providing dual mechanisms to support learned behavior acquisition during cognitive task performance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Abnormal flexor carpi radialis H-reflex as a specific indicator of C7 as compared with C6 radiculopathy.

PubMed

Zheng, Chaojun; Zhu, Yu; Lv, Feizhou; Ma, Xiaosheng; Xia, Xinlei; Wang, Lixun; Jin, Xiang; Weber, Robert; Jiang, Jianyuan; Anuvat, Kevin

2014-12-01

The H-reflex of the flexor carpi radialis (FCR H-reflex) has not been commonly used for the diagnosis of cervical radiculopathy when compared with the routinely tested soleus H-reflex. Although both S1 and S2 roots innervate the soleus, the H-reflex is selectively related to S1 nerve root function clinically. Flexor carpi radialis is also innervated by two nerve roots which are C6 and C7. Although they are among the most common roots involved in cervical radiculopathy, few studies reported if the attenuation of the FCR H-reflex is caused by lesions affecting C7 or C6 nerve roots, or both. We aimed to identify whether an abnormal FCR H-reflex was attributed to the C7 or C6 nerve root lesion, or both. The sensitivities of needle electromyography, FCR H-reflex, and provocative tests in unilateral C7 or C6 radiculopathy were also compared in this study. A concentric needle electrode recorded bilateral FCR H-reflexes in 41 normal subjects (control group), 51 patients with C7 radiculopathy, and 54 patients with C6 radiculopathy. Clinical, radiological, and surgical approaches identified the precise single cervical nerve root involved in all patient groups. The H-reflex and M-wave latencies were measured and compared bilaterally. Abnormal FCR H-reflex was defined as the absence of the H-reflex or a side-to-side difference over 1.5 milliseconds which was based on the normal side-to-side difference of the H-reflex latency of 16.9 milliseconds (SD = 1.7 milliseconds) from the control group. We also determined standard median and ulnar conduction and needle electromyography. The provocative tests included bilateral determination of the Shoulder Abduction and Spurling's tests in all radiculopathy group patients. Abnormal FCR H-reflexes were recorded in 45 (88.2%) of C7 radiculopathy group patients, and 2 (3.7%) of C6 radiculopathy group patients (P < 0.05). Needle electromyography was abnormal in 41 (80.4%) of C7 radiculopathy patients and 43 (79.6%) of C6 radiculopathy patients. Provocative tests were positive in 15 (29.4%) of C7 radiculopathy patients and 25 (46.3%) of C6 radiculopathy patients. Flexor carpi radialis H-Reflex provides a sensitive assessment of evaluating the C7 spinal reflex pathway. Clinically, a combination of the FCR H-reflex with needle electromyography may yield the highest level of diagnostic information for evaluating clinical cases of C7 radiculopathy.

Acetylcholine released from cholinergic nerves contributes to cutaneous vasodilation during heat stress

NASA Technical Reports Server (NTRS)

Shibasaki, Manabu; Wilson, Thad E.; Cui, Jian; Crandall, Craig G.

2002-01-01

Nitric oxide (NO) contributes to active cutaneous vasodilation during a heat stress in humans. Given that acetylcholine is released from cholinergic nerves during whole body heating, coupled with evidence that acetylcholine causes vasodilation via NO mechanisms, it is possible that release of acetylcholine in the dermal space contributes to cutaneous vasodilation during a heat stress. To test this hypothesis, in seven subjects skin blood flow (SkBF) and sweat rate were simultaneously monitored over three microdialysis membranes placed in the dermal space of dorsal forearm skin. One membrane was perfused with the acetylcholinesterase inhibitor neostigmine (10 microM), the second membrane was perfused with the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME; 10 mM) dissolved in the aforementioned neostigmine solution (l-NAME(Neo)), and the third membrane was perfused with Ringer solution as a control site. Each subject was exposed to approximately 20 min of whole body heating via a water-perfused suit, which increased mean body temperature from 36.4 +/- 0.1 to 37.5 +/- 0.1 degrees C (P < 0.05). After the heat stress, SkBF at each site was normalized to its maximum value, identified by administration of 28 mM sodium nitroprusside. Mean body temperature threshold for cutaneous vasodilation was significantly lower at the neostigmine-treated site relative to the other sites (neostigmine: 36.6 +/- 0.1 degrees C, l-NAME(Neo): 37.1 +/- 0.1 degrees C, control: 36.9 +/- 0.1 degrees C), whereas no significant threshold difference was observed between the l-NAME(Neo)-treated and control sites. At the end of the heat stress, SkBF was not different between the neostigmine-treated and control sites, whereas SkBF at the l-NAME(Neo)-treated site was significantly lower than the other sites. These results suggest that acetylcholine released from cholinergic nerves is capable of modulating cutaneous vasodilation via NO synthase mechanisms early in the heat stress but not after substantial cutaneous vasodilation.

Alternative splicing in nicotinic acetylcholine receptor subunits from Locusta migratoria and its influence on acetylcholine potencies.

PubMed

Zhang, Yixi; Liu, Yang; Bao, Haibo; Sun, Huahua; Liu, Zewen

2017-01-18

Due to the great abundance within insect central nervous system (CNS), nicotinic acetylcholine receptors (nAChRs) play key roles in insect CNS, which makes it to be the targets of several classes of insecticides, such as neonicotinoids. Insect nAChRs are pentameric complexes consisting of five subunits, and a dozen subunits in one insect species can theoretically comprise diverse nAChRs. The alternative splicing in insect nAChR subunits may increase the diversity of insect nAChRs. In the oriental migratory locust (Locusta migratoria manilensis Meyen), a model insect species with agricultural importance, the alternative splicing was found in six α subunits among nine α and two β subunits, such as missing conserved residues in Loop D from Locα1, Locα6 and Locα9, a 34-residue insertion in Locα8 cytoplasmic loop, and truncated transcripts for Locα4, Locα7 and Locα9. Hybrid nAChRs were successfully constructed in Xenopus oocytes through co-expression with rat β2 and one α subunit from L. migratoria, which included Locα1, Locα2, Locα3, Locα4, Locα5, Locα8 and Locα9. Influences of alternative splicing in Locα1, Locα8 and Locα9 on acetylcholine potency were tested on hybrid nAChRs. The alternative splicing in Locα1 and Locα9 could increase acetylcholine sensitivities on recombinant receptors, while the splicing in Locα8 showed significant influences on the current amplitudes of oocytes. The results revealed that the alternative splicing at or close to the ligand-binding sites, as well as at cytoplasmic regions away from the ligand-binding sites, in insect nAChR subunits would change the agonist potencies on the receptors, which consequently increased nAChR diversity in functional and pharmacological properties. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Inhibitory effects of pine nodule extract and its component, SJ-2, on acetylcholine-induced catecholamine secretion and synthesis in bovine adrenal medullary cells.

PubMed

Li, Xiaojia; Horishita, Takafumi; Toyohira, Yumiko; Shao, Hui; Bai, Jie; Bo, Haixia; Song, Xinbo; Ishikane, Shin; Yoshinaga, Yukari; Satoh, Noriaki; Tsutsui, Masato; Yanagihara, Nobuyuki

2017-04-01

Extract of pine nodules (matsufushi) formed by bark proliferation on the surface of trees of Pinus tabulaeformis or Pinus massoniana has been used as an analgesic for joint pain, rheumatism, neuralgia, dysmenorrhea and other complaints in Chinese traditional medicine. Here we report the effects of matsufushi extract and its components on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. We found that matsufushi extract (0.0003-0.005%) and its component, SJ-2 (5-hydroxy-3-methoxy-trans-stilbene) (0.3-100 μM), but not the other three, concentration-dependently inhibited catecholamine secretion induced by acetylcholine, a physiological secretagogue. Matsufushi extract (0.0003-0.005%) and SJ-2 (0.3-100 μM) also inhibited 45 Ca 2+ influx induced by acetylcholine in a concentration-dependent manner, similar to its effect on catecholamine secretion. They also suppressed 14 C-catecholamine synthesis and tyrosine hydroxylase activity induced by acetylcholine. In Xenopus oocytes expressing α3β4 nicotinic acetylcholine receptors, matsufushi extract (0.00003-0.001%) and SJ-2 (1-100 μM) directly inhibited the current evoked by acetylcholine. The present findings suggest that SJ-2, as well as matsufushi extract, inhibits acetylcholine-induced catecholamine secretion and synthesis by suppression of nicotinic acetylcholine receptor-ion channels in bovine adrenal medullary cells. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Acetylcholine protects mesenteric arteries against hypoxia/reoxygenation injury via inhibiting calcium-sensing receptor.

PubMed

Zhao, Ming; He, Xi; Yang, Yong-Hua; Yu, Xiao-Jiang; Bi, Xue-Yuan; Yang, Yang; Xu, Man; Lu, Xing-Zhu; Sun, Qiang; Zang, Wei-Jin

2015-04-01

The Ca(2+)-sensing receptor (CaSR) plays an important role in regulating vascular tone. In the present study, we investigated the positive effects of the vagal neurotransmitter acetylcholine by suppressing CaSR activation in mesenteric arteries exposed to hypoxia/reoxygenation (H/R). The artery rings were exposed to a modified 'ischemia mimetic' solution and an anaerobic environment to simulate an H/R model. Our results showed that acetylcholine (10(-6) mol/L) significantly reduced the contractions induced by KCl and phenylephrine and enhanced the endothelium-dependent relaxation induced by acetylcholine. Additionally, acetylcholine reduced CaSR mRNA expression and activity when the rings were subjected to 4 h of hypoxia and 12 h of reoxygenation. Notably, the CaSR antagonist NPS2143 significantly reduced the contractions but did not improve the endothelium-dependent relaxation. When a contractile response was achieved with extracellular Ca(2+), both acetylcholine and NPS2143 reversed the H/R-induced abnormal vascular vasoconstriction, and acetylcholine reversed the calcimimetic R568-induced abnormal vascular vasoconstriction in the artery rings. In conclusion, this study suggests that acetylcholine ameliorates the dysfunctional vasoconstriction of the arteries after H/R, most likely by decreasing CaSR expression and activity, thereby inhibiting the increase in intracellular calcium concentration. Our findings may be indicative of a novel mechanism underlying ACh-induced vascular protection. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Acetylcholine content and viability of cholinergic neurons are influenced by the activity of protein histidine phosphatase

PubMed Central

2012-01-01

Background The first mammalian protein histidine phosphatase (PHP) was discovered in the late 90s of the last century. One of the known substrates of PHP is ATP-citrate lyase (ACL), which is responsible - amongst other functions - for providing acetyl-CoA for acetylcholine synthesis in neuronal tissues. It has been shown in previous studies that PHP downregulates the activity of ACL by dephosphorylation. According to this our present work focused on the influence of PHP activity on the acetylcholine level in cholinergic neurons. Results The amount of PHP in SN56 cholinergic neuroblastoma cells was increased after overexpression of PHP by using pIRES2-AcGFP1-PHP as a vector. We demonstrated that PHP overexpression reduced the acetylcholine level and induced cell death. The acetylcholine content of SN56 cells was measured by fast liquid chromatography-tandem mass spectrometry method. Overexpression of the inactive H53A-PHP mutant also induced cell damage, but in a significantly reduced manner. However, this overexpression of the inactive PHP mutant did not change the acetylcholine content of SN56 cells significantly. In contrast, PHP downregulation, performed by RNAi-technique, did not induce cell death, but significantly increased the acetylcholine content in SN56 cells. Conclusions We could show for the first time that PHP downregulation increased the acetylcholine level in SN56 cells. This might be a potential therapeutic strategy for diseases involving cholinergic deficits like Alzheimer's disease. PMID:22436051

Ameliorative effect of Noni fruit extract on streptozotocin-induced memory impairment in mice.

PubMed

Pachauri, Shakti D; Verma, Priya Ranjan P; Dwivedi, Anil K; Tota, Santoshkumar; Khandelwal, Kiran; Saxena, Jitendra K; Nath, Chandishwar

2013-08-01

This study evaluated the effects of a standardized ethyl acetate extract of Morinda citrifolia L. (Noni) fruit on impairment of memory, brain energy metabolism, and cholinergic function in intracerebral streptozotocin (STZ)-treated mice. STZ (0.5 mg/kg) was administered twice at an interval of 48 h. Noni (50 and 100 mg/kg, postoperatively) was administered for 21 days following STZ administration. Memory function was evaluated using Morris Water Maze and passive avoidance tests, and brain levels of cholinergic function, oxidative stress, energy metabolism, and brain-derived neurotrophic factor (BDNF) were estimated. STZ caused memory impairment in Morris Water Maze and passive avoidance tests along with reduced brain levels of ATP, BDNF, and acetylcholine and increased acetylcholinesterase activity and oxidative stress. Treatment with Noni extract (100 mg/kg) prevented the STZ-induced memory impairment in both behavioral tests along with reduced oxidative stress and acetylcholinesterase activity, and increased brain levels of BDNF, acetylcholine, and ATP level. The study shows the beneficial effects of Noni fruit against STZ-induced memory impairment, which may be attributed to improved brain energy metabolism, cholinergic neurotransmission, BDNF, and antioxidative action.

Does the medical diagnosis of occupational asthma coincide with the legal diagnosis?

PubMed

Çelebi Sözener, Zeynep; Aydın, Ömür; Demirel, Yavuz Selim; Soyyiğit, Şadan; Çerçi, Pamir; Kendirlinan, Reşat; Bavbek, Sevim; Çelik, Gülfem Elif; Misirligil, Zeynep; Sin, Betül Ayşe; Keleşoğlu, Arif; Mungan, Dilşad

2017-11-01

The incidence of occupational asthma (OA) is increasing worldwide. In this study, we first aimed to document the rate of diagnosis of OA among patients who were referred to our clinic from the Social Security Institution and the factors that affected diagnosis; secondly, we aimed to assess the consistency of the medical and legal diagnoses. The study involved 132 consecutive patients who were referred to our clinic for the evaluation of OA between 2010 and 2015. Detailed workplace history, the tools used in the diagnosis such as peak expiratory flow (PEF) monitoring and bronchial provocation tests, and the final medical diagnosis were recorded from case files. Asthma was diagnosed in 75% (n = 99) of the patients. Among them, 22.2% were diagnosed as having OA. The diagnosis was confirmed by serial PEF measurements, non-specific bronchial hyperreactivity assessment or both of the tests both at work and off-work periods. OA diagnosis was mostly established in active workers (72.7%). The legal diagnosis period was completed in 54.5% of these 22 patients, and 50% (n = 11) were officially diagnosed as having OA with a 91.6% concordance with medical diagnosis. This study verifies the importance of diagnosing asthma correctly as a first step in the evaluation of OA. Diagnostic tests other than specific provocation tests could be preferential in patients who still work in the same field. We believe that cooperation with the patient's occupational physician and adequate recognition of the work environment will improve the consistency of legal and medical diagnoses.

Individual differences in responses to provocation and frequent victimization by peers.

PubMed

Champion, Kelly M; Clay, Daniel L

2007-02-01

This study examined associations between victimization by peers and intention to respond to provocative events as a function of anger arousal and motivation to improve the situation in a cross-sectional sample of school-age children (N = 506, 260 males, 246 females). Results demonstrated that more intense anger and more retaliatory motivation were positively associated with intentions to aggress and with frequency of victimization. The association between aggressive intentions to respond to anger provocation and victimization could be accounted for by subjective feelings of anger and motivation to retaliate. The contribution of emotion processes was stronger for boys than for girls. A post hoc examination of non-bullying participants revealed that motivation accounted for aggressive intentions among the non-bullies. Results support including anger management programs in prevention efforts that target the school climate and victims' risk for psychopathology.

Biochemical correlates of neurosensory changes in weightlessness

NASA Technical Reports Server (NTRS)

Leach, Carolyn S.; Reschke, Millard F.

1989-01-01

The possible existence of a relationship between space motion sickness and chemical and biochemical variables measured in body fluids is studied. Clinical chemistry and endocrine measurements from blood and urine samples taken before and after Space Shuttle flights were analyzed along with the occurrence of SMS during flight and provocative testing before flight. Significant positive correlations were observed with serum chloride and significant negative correlations with serum phosphate, serum uric acid, and plasma thyroid stimulating hormone.

Nicotinic Acetylcholine Receptors in Sensory Cortex

ERIC Educational Resources Information Center

Metherate, Raju

2004-01-01

Acetylcholine release in sensory neocortex contributes to higher-order sensory function, in part by activating nicotinic acetylcholine receptors (nAChRs). Molecular studies have revealed a bewildering array of nAChR subtypes and cellular actions; however, there is some consensus emerging about the major nAChR subtypes and their functions in…

Televised relational and physical aggression and children's hostile intent attributions.

PubMed

Martins, Nicole

2013-12-01

An experiment was conducted with 150 children (mean age=10.1years) in third to fifth grades to test whether exposure to different forms of aggression in the media affected hostile attributional biases in response to different forms of provocation scenarios. Children were randomly assigned to watch a clip containing physical aggression, relational aggression, or no aggression. After exposure, children were asked to respond to a series of written provocation scenarios where a character caused some form of harm (instrumental or relational) to a target person, but the intent of the provocateur was ambiguous. Results revealed that exposure to relationally aggressive portrayals resulted in a hostile attributional bias in response to relational scenarios, whereas exposure to portrayals of physical aggression was associated with a hostile attributional bias in response to instrumental scenarios. Moreover, these biases were shown to be specific to the exposure condition (physical or relational) and not simply associated with exposure to aggression in general. The findings are discussed in terms of the general aggression model and children's social information processing. Copyright © 2013 Elsevier Inc. All rights reserved.

Mobile kidney pain provocation ultrasonography before surgery for symptomatic mobile kidney: A prospective study of 43 consecutive patients.

PubMed

Arnerlöv, Conny; Söderström, Minette; Öhberg, Lars

2016-01-01

The aim of this study was to evaluate whether mobile kidney pain provocation ultrasonography together with intravenous pyelography in supine and standing positions and a full medical history can confirm the diagnosis of the clinical condition of symptomatic mobile kidney and aid the selection of patients for surgical treatment. In a consecutive study, 43 patients with the clinical picture of symptomatic mobile kidney, a positive mobile kidney pain provocation ultrasonography and a renal descent of at least 2 lumbar vertebral heights on intravenous pyelography in the standing position, were operated on with nephropexy. Patients' pain relief after nephropexy was evaluated by clinical follow-up, a questionnaire and visual analogue scale (VAS) scoring. Reduction of pain after nephropexy was associated with a significant decrease in VAS scoring from a median of 8 (range 4-10) preoperatively to a median of 0 (range 0-7) postoperatively (p < 0.001). Thirty-four patients (79%) were cured of their pain and seven patients (16%) experienced substantial relief from their pain symptoms. In two patients (5%) the symptoms were unchanged. The results indicate that mobile kidney pain provocation ultrasonography and intravenous pyelography in supine and standing positions can verify the diagnosis of symptomatic mobile kidney and aid the selection of patients who will benefit from nephropexy.

State narcissism and aggression: The mediating roles of anger and hostile attributional bias.

PubMed

Li, Caina; Sun, Ying; Ho, Man Yee; You, Jin; Shaver, Phillip R; Wang, Zhenhong

2016-07-01

Prior research has documented a relationship between narcissism and aggression but has focused only on dispositional narcissism without considering situational factors that may increase narcissism temporarily. This study explored the possibility that an increase in state narcissism would foster aggressive responding by increasing anger and hostile attributional bias following unexpected provocation among 162 college students from China. We created a guided-imagination manipulation to heighten narcissism and investigated its effects on anger, aroused hostile attribution bias, and aggressive responses following a provocation with a 2 (narcissism/neutral manipulation) × 2 (unexpected provocation/positive evaluation condition) between-subjects design. We found that the manipulation did increase self-reported state narcissism. The increase in state narcissism in turn heightened aggression, and this relation was mediated by increased anger. Regardless of the level of state narcissism, individuals were more aggressive after being provoked and this effect of provocation was mediated by hostile attributional bias. The findings indicate that narcissism can be temporarily heightened in a nonclinical sample of individuals, and that the effect of state narcissism on aggression is mediated by anger. Differences between state and trait narcissism and possible influences of culture are discussed. Aggr. Behav. 42:333-345, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

An anti-nicotinic cognitive challenge model using mecamylamine in comparison with the anti-muscarinic cognitive challenge using scopolamine.

PubMed

Baakman, Anne Catrien; Alvarez-Jimenez, Ricardo; Rissmann, Robert; Klaassen, Erica S; Stevens, Jasper; Goulooze, Sebastiaan C; den Burger, Jeroen C G; Swart, Eleonora L; van Gerven, Joop M A; Groeneveld, Geert Jan

2017-08-01

The muscarinic acetylcholine receptor antagonist scopolamine is often used for proof-of-pharmacology studies with pro-cognitive compounds. From a pharmacological point of view, it would seem more rational to use a nicotinic rather than a muscarinic anticholinergic challenge to prove pharmacology of a nicotinic acetylcholine receptor agonist. This study aims to characterize a nicotinic anticholinergic challenge model using mecamylamine and to compare it to the scopolamine model. In this double-blind, placebo-controlled, four-way cross-over trial, 12 healthy male subjects received oral mecamylamine 10 and 20 mg, intravenous scopolamine 0.5 mg and placebo. Pharmacokinetics were analysed using non-compartmental analysis. Pharmacodynamic effects were measured with a multidimensional test battery that includes neurophysiological, subjective, (visuo)motor and cognitive measurements. All treatments were safe and well tolerated. Mecamylamine had a t max of 2.5 h and a C max of 64.5 ng ml -1 for the 20 mg dose. Mecamylamine had a dose-dependent effect decreasing the adaptive tracking performance and VAS alertness, and increasing the finger tapping and visual verbal learning task performance time and errors. Scopolamine significantly affected almost all pharmacodynamic tests. This study demonstrated that mecamylamine causes nicotinic receptor specific temporary decline in cognitive functioning. Compared with the scopolamine model, pharmacodynamic effects were less pronounced at the dose levels tested; however, mecamylamine caused less sedation. The cognitive effects of scopolamine might at least partly be caused by sedation. Whether the mecamylamine model can be used for proof-of-pharmacology of nicotinic acetylcholine receptor agonists remains to be established. © 2017 The British Pharmacological Society.

Colonoscopic allergen provocation test with rBet v 1 in patients with pollen-associated food allergy.

PubMed

Pickert, C N; Lorentz, A; Manns, M P; Bischoff, S C

2012-10-01

After consumption of fruits, nuts, and vegetables, several patients with pollen allergy experience gastrointestinal (GI) tract symptoms that are possibly caused by pollen-associated food allergy. The aim of this study was to evaluate the colonoscopic allergen provocation (COLAP) test using the recombinant birch pollen allergen Bet v 1 (rBet v 1) for in vivo diagnosis of pollen-associated food allergy manifesting in the GI tract. Thirty-four patients with a history of adverse reactions to food, GI tract symptoms, and birch pollen pollinosis and five healthy controls underwent COLAP test. Twenty minutes after endoscopic challenge of the cecal mucosa with rBet v 1, the mucosal wheal and flare reaction was registered semiquantitatively, and tissue biopsy specimens were examined for eosinophil mucosal activation. The mucosal reaction to rBet v 1 was correlated with the presence of pollinosis (P = 0.004), history of adverse reaction to Bet v 1-associated food allergens (P = 0.001), and tissue eosinophils' activation (P < 0.001). A wheal and flare reaction in the COLAP test was observed in 13 of 16 patients (81%) with a history of GI tract symptoms associated with the ingestion of Bet v 1-related foods and in four of 18 (22%) patients with a negative history (P < 0.001). The control group did not develop visible mucosal reactions to rBet v 1. Systemic anaphylactic reactions did not occur. The mucosal administration of rBet v 1 by COLAP test provides a new diagnostic tool that might support the diagnosis of Bet v 1-associated food allergy manifesting in the GI tract. © 2012 John Wiley & Sons A/S.

A critique of a UK standardized test of finger rewarming after cold provocation in the diagnosis and staging of hand-arm vibration syndrome.

PubMed

Mason, H J; Poole, K; Saxton, J

2003-08-01

Accurate diagnosis and staging of hand-arm vibration syndrome (HAVS) is important in health surveillance of vibration-exposed workers and the substantial number of related medico-legal cases. The measurement of the rewarming rate of fingers after cold provocation to the hands (CPT) has been suggested as a useful test in diagnosing HAVS. To investigate the diagnostic value of a standardized version of the CPT test using a 15 degrees C cold challenge for 5 min applied in the recent compensation assessment of UK miners. Analysis of a subset of UK miners assessed at our unit, together with data from a small repeatability study of the standardized CPT in normal subjects. Rewarming time in the CPT was significantly lower in those subjects classified as vascular Stockholm stage 0 compared with Stockholm stages 1-3 combined, but did not discriminate between the stages of abnormality. Using the suggested cut-off in the CPT test, the sensitivity and specificity were calculated as 43 and 78%, respectively. Receiver operator characteristic analysis suggested that the rewarming time of highest accuracy gave a sensitivity of 66% and specificity of 59%. In 10 miners who reported unilateral hand blanching, there was no significant difference in CPT measurements between blanching and non-blanching hands. Repeat CPT measurements in normal subjects suggested mean differences of 52 and 107 s for each hand, and the Bland-Altman coefficient of repeatability was approximately 600 s for all fingers. Single application of this standardized CPT test may have limited value in diagnosing the vascular component of HAVS in an individual.

Prospective assessment of diagnostic tests for pediatric penicillin allergy, from clinical history to challenge tests✰,✰✰,✰✰✰.

PubMed

Ibáñez, María Dolores; Del Río, Pablo Rodríguez; Lasa, Eva Maria; Joral, Alejandro; Ruiz-Hornillos, Javier; Muñoz, Candelaria; Traseira, Carmen Gómez; Escudero, Carmelo; Olaguibel Rivera, Jose María; Garriga-Baraut, Teresa; González-de-Olano, David; Rosado, Ana; Sanchez-García, Silvia; Bustamante, Socorro Pérez; Vilchez, Maria Antonia Padial; Montaño, Patricia Prieto; Morillo, Rocío Candón; Iglesia, Eva Macías; Vila, Angélica Feliú; Valbuena, Teresa; Lopez-Patiño, Ana; Martorell, Antonio; Sastre, Joaquín; Audícana, María Teresa

2018-05-24

Diagnostic guidelines for penicillin allergy in children recommend cumbersome protocols based partially on data from adults, which may be suboptimal for pediatric use. To assess the accuracy of tools for diagnosis of penicillin allergy in children. A prospective multicenter study was conducted in children with reported adverse events related to penicillin, excluding severe reactions. All patients underwent a uniform diagnostic protocol consisting of clinical history, skin tests, serum specific IgE, and, regardless of these results, drug provocation tests (DPT). 732 children (mean 5.5 years; 51.2% males) completed the allergy work-up, including DPT. Amoxicillin triggered 96.9% of all reactions. None of the patients with an immediate index reaction (IR) developed a reaction on DPT. Penicillin allergy was confirmed in 35 subjects (4.8%): 6(17%) immediate and 29(83%) non-immediate reactions in the DPT. No severe reactions were recorded. The allergist diagnosis based upon the clinical history was not associated with the final outcome at DPT. In 30 of 33(91%) allergic patients, all skin tests and sIgE were negative. A logistic regression model identified the following to be associated with PNC allergy (p<0.05): a family history of drug allergy (OR=3.03; 95% confidence interval (CI): 1.33-6.89), an IR lasting >3 days vs ≤24 hours (OR=8.96; 95% CI: 2.01-39.86), and IR while receiving corticosteroids (OR=2.68; 95% CI: 1.30-5.54). Conventional predictors of allergy to penicillin performed weakly. The authors propose straightforward penicillin provocation testing in controlled, experienced centers for the diagnosis of non-severe penicillin allergy in children. Copyright © 2018. Published by Elsevier Inc.

Responses of dogs with food allergies to single-ingredient dietary provocation.

PubMed

Jeffers, J G; Meyer, E K; Sosis, E J

1996-08-01

To characterize specific food ingredients causing allergic reactions in dogs and to assess cross-reactivity between proteins derived from a single animal source or from different plant products. Prospective study. 25 dogs with histories and cutaneous signs consistent with food-allergic dermatitis. Dogs were fed a food-elimination diet until resolution of clinical signs and then challenged with their original diet. A diagnosis of food allergy was made if there was complete return of pruritus within 14 days of challenge exposure. After diagnosis, dogs were fed the food-elimination diet until signs related to dietary challenge abated. The dogs then were fed beef, chicken, chicken eggs, cows' milk, wheat, soy, and corn in single-ingredient provocation trials for 1 week. Any cutaneous reactions to these food ingredients were recorded by their owners. Beef and soy most often caused adverse cutaneous reactions, although all ingredients induced clinical signs in at least 1 dog. Mean number of allergens per dog was 2.4, with 80% reacting to 1 or 2 proteins and 64% reacting to 2 or more of the proteins tested. A significant difference was found between dogs reacting to beef versus cows' milk and between dogs reacting to soy versus wheat; thus, the hypothesis of cross-reactivity to ingredients derived from a single animal source or to different plant products was not supported. Similar differences between chicken meat and eggs were not identified. Long-term management of dogs with food allergies is facilitated by identification of the most commonly encountered food allergens. Because cross-reactivity cannot be verified, each protein source should be included separately in food-provocation trials.

Cybersickness provoked by head-mounted display affects cutaneous vascular tone, heart rate and reaction time.

PubMed

Nalivaiko, Eugene; Davis, Simon L; Blackmore, Karen L; Vakulin, Andrew; Nesbitt, Keith V

2015-11-01

Evidence from studies of provocative motion indicates that motion sickness is tightly linked to the disturbances of thermoregulation. The major aim of the current study was to determine whether provocative visual stimuli (immersion into the virtual reality simulating rides on a rollercoaster) affect skin temperature that reflects thermoregulatory cutaneous responses, and to test whether such stimuli alter cognitive functions. In 26 healthy young volunteers wearing head-mounted display (Oculus Rift), simulated rides consistently provoked vection and nausea, with a significant difference between the two versions of simulation software (Parrot Coaster and Helix). Basal finger temperature had bimodal distribution, with low-temperature group (n=8) having values of 23-29 °C, and high-temperature group (n=18) having values of 32-36 °C. Effects of cybersickness on finger temperature depended on the basal level of this variable: in subjects from former group it raised by 3-4 °C, while in most subjects from the latter group it either did not change or transiently reduced by 1.5-2 °C. There was no correlation between the magnitude of changes in the finger temperature and nausea score at the end of simulated ride. Provocative visual stimulation caused prolongation of simple reaction time by 20-50 ms; this increase closely correlated with the subjective rating of nausea. Lastly, in subjects who experienced pronounced nausea, heart rate was elevated. We conclude that cybersickness is associated with changes in cutaneous thermoregulatory vascular tone; this further supports the idea of a tight link between motion sickness and thermoregulation. Cybersickness-induced prolongation of reaction time raises obvious concerns regarding the safety of this technology. Copyright © 2015 Elsevier Inc. All rights reserved.

Teens With Heavy Prenatal Cocaine Exposure Respond to Experimental Social Provocation with Escape Not Aggression

PubMed Central

Greenwald, M.K.; Chiodo, L.M.; Hannigan, J.H.; Sokol, R.J.; Janisse, J.; Delaney-Black, V.

2010-01-01

Preclinical data show that, compared to no exposure, prenatal cocaine exposure (PCE) has age-dependent effects on social interaction and aggression. The aim of this clinical study was to determine how heavy/persistent PCE – after controlling for other prenatal drug exposures, sex and postnatal factors – predicts behavioral sensitivity to provocation (i.e., reactive aggression) using a well-validated human laboratory model of aggression. African American teens (mean = 14.2 yrs old) with histories of heavy/persistent PCE (maternal cocaine use ≥ 2 times/week during pregnancy, or positive maternal or infant urine/meconium test at delivery; n = 86) or none/some exposure (NON: maternal cocaine use < 2 times/week during pregnancy; n = 330) completed the Point Subtraction Aggression Paradigm. In this task, teens competed in a computer game against a fictitious opponent. There were three possible responses: (a) earn points, to exchange for money later; or (b) “aggress” against the fictitious opponent by subtracting their points; or (c) escape temporarily from point subtraction perpetrated by the fictitious opponent. The PCE group responded significantly more frequently on the escape option than the NON group, but did not differ in aggressive or money-earning responses. These data indicate that PCE-teens provoked with a social stressor exhibit a behavioral preference for escape (negative reinforcement) more than for aggressive (retaliatory) or appetitive (point- or money-reinforced) responses. These findings are consistent with preclinical data showing that social provocation of adolescent or young adult offspring after PCE is associated with greater escape behavior, inferring greater submission, social withdrawal, or anxiety, as opposed to aggressive behavior. PMID:20600841

Mixed nicotinic-muscarinic properties of the alpha9 nicotinic cholinergic receptor.

PubMed

Verbitsky, M; Rothlin, C V; Katz, E; Elgoyhen, A B

2000-10-01

The rat alpha9 nicotinic acetylcholine receptor (nAChR) was expressed in Xenopus laevis oocytes and tested for its sensitivity to a wide variety of cholinergic compounds. Acetylcholine (ACh), carbachol, choline and methylcarbachol elicited agonist-evoked currents, giving maximal or near maximal responses. Both the nicotinic agonist suberyldicholine as well as the muscarinic agonists McN-A-343 and methylfurtrethonium behaved as weak partial agonists of the receptor. Most classical cholinergic compounds tested, being either nicotinic (nicotine, epibatidine, cytisine, methyllycaconitine, mecamylamine, dihydro-beta-erythroidine), or muscarinic (muscarine, atropine, gallamine, pilocarpine, bethanechol) agonists and antagonists, blocked the recombinant alpha9 receptor. Block by nicotine, epibatidine, cytisine, methyllycaconitine and atropine was overcome at high ACh concentrations, suggesting a competitive type of block. The present results indicate that alpha9 displays mixed nicotinic-muscarinic features that resemble the ones described for the cholinergic receptor of cochlear outer hair cells (OHCs). We suggest that alpha9 contains the structural determinants responsible for the pharmacological properties of the native receptor.

Test-retest paradigm of the forced swimming test in female mice is not valid for predicting antidepressant-like activity: participation of acetylcholine and sigma-1 receptors.

PubMed

Su, Jing; Hato-Yamada, Noriko; Araki, Hiroaki; Yoshimura, Hiroyuki

2013-01-01

The forced swimming test (FST) in mice is widely used to predict the antidepressant activity of a drug, but information describing the immobility of female mice is limited. We investigated whether a prior swimming experience affects the immobility duration in a second FST in female mice and whether the test-retest paradigm is a valid screening tool for antidepressants. Female ICR mice were exposed to the FST using two experimental paradigms: a single FST and a double FST in which mice had experienced FST once 24 h prior to the second trail. The initial FST experience reliably prolonged immobility duration in the second FST. The antidepressants imipramine and paroxetine significantly reduced immobility duration in the single FST, but not in the double FST. Scopolamine and the sigma-1 (σ1) antagonist NE-100 administered before the second trial significantly prevented the prolongation of immobility. Neither a 5-HT1A nor a 5-HT2A receptor agonist affected immobility duration. We suggest that the test-retest paradigm in female mice is not adequate for predicting antidepressant-like activity of a drug; the prolongation of immobility in the double FST is modulated through acetylcholine and σ1 receptors.

Sigma receptor ligand N,N'-di-(ortho-tolyl)guanidine inhibits release of acetylcholine in the guinea pig ileum.

PubMed

Cambell, B G; Keana, J F; Weber, E

1991-11-26

The inhibition of stimulated contractions of the guinea pig ileum longitudinal muscle/myenteric plexus preparation by sigma receptor ligands has been previously described. In this study, the stimulated release of [3H]acetylcholine from cholinergic nerve terminals in this same preparation was monitored in the presence and absence of sigma receptor ligands. N,N'-Di-(orthotolyl)guanidine (DTG) and other compounds selective for the sigma receptor inhibited stimulated [3H]acetylcholine release. These results suggest that their inhibition of stimulated contractions in this preparation was mediated by inhibition of acetylcholine release.

Hostile attribution biases for relationally provocative situations and event-related potentials.

PubMed

Godleski, Stephanie A; Ostrov, Jamie M; Houston, Rebecca J; Schlienz, Nicolas J

2010-04-01

This exploratory study investigates how hostile attribution biases for relationally provocative situations may be related to neurocognitive processing using the P300 event-related potential. Participants were 112 (45 women) emerging adults enrolled in a large, public university in upstate New York. Participants completed self-report measures on relational aggression and hostile attribution biases and performed an auditory perseveration task to elicit the P300. It was found that hostile attribution biases for relational provocation situations was associated with a larger P300 amplitude above and beyond the role of hostile attribution biases for instrumental situations, relational aggression, and gender. Larger P300 amplitude is interpreted to reflect greater allocation of cognitive resources or enhanced "attending" to salient stimuli. Implications for methodological approaches to studying aggression and hostile attribution biases and for theory are discussed, as well as implications for the fields of developmental psychology and psychopathology. Copyright 2010 Elsevier B.V. All rights reserved.

Carpal tunnel syndrome – Part I (anatomy, physiology, etiology and diagnosis)☆☆☆

PubMed Central

Chammas, Michel; Boretto, Jorge; Burmann, Lauren Marquardt; Ramos, Renato Matta; dos Santos Neto, Francisco Carlos; Silva, Jefferson Braga

2014-01-01

Carpal tunnel syndrome (CTS) is defined by compression of the median nerve in the wrist. It is the commonest of the compressive syndromes and its most frequent cause is idiopathic. Even though spontaneous regression is possible, the general rule is that the symptoms will worsen. The diagnosis is primarily clinical, from the symptoms and provocative tests. Electroneuromyographic examination may be recommended before the operation or in cases of occupational illnesses. PMID:26229841

Cutaneous microvascular response during local cold exposure - the effect of female sex hormones and cold perception.

PubMed

Cankar, Ksenija; Music, Mark; Finderle, Zare

2016-11-01

It is generally known that differences exist between males and females with regard to sensitivity to cold. Similar differences even among females in different hormonal balance might influence microvascular response during cold provocation testing. The aim of the present study was to measure sex hormone levels, cold and cold pain perception thresholds and compare them to cutaneous laser-Doppler flux response during local cooling in both the follicular and luteal phases of the menstrual cycle. In the luteal phase a more pronounced decrease in laser-Doppler flux was observed compared to follicular phase during local cooling at 15°C (significant difference by Dunnett's test, p<0.05). In addition, statistically significant correlations between progesterone level and laser-Doppler flux response to local cooling were observed during the follicular (R=-0.552, p=0.0174) and during the luteal phases (R=0.520, p=0.0271). In contrast, the correlation between estradiol level and laser-Doppler flux response was observed only in the follicular phase (R=-0.506, p=0.0324). Our results show that individual sensitivity to cold influences cutaneous microvascular response to local cooling; that microvascular reactivity is more pronounced during the luteal phase of the menstrual cycle; and that reactivity correlates with hormone levels. The effect of specific sex hormone levels is related to the cold-provocation temperature. Copyright © 2016. Published by Elsevier Inc.

M.I.T./Canadian vestibular experiments on the Spacelab-1 mission: 4. Space motion sickness: symptoms, stimuli, and predictability

NASA Technical Reports Server (NTRS)

Oman, C. M.; Lichtenberg, B. K.; Money, K. E.; McCoy, R. K.

1986-01-01

Space sickness symptoms were observed by 4 specially trained observers on Spacelab-1. Three reported persistent symptoms, and vomited repeatedly during the first and/or second day of flight. Head movements on all axes were provocative, particularly in pitch and roll. Head acceleration data recorded from 2 symptomatic crewmen showed that after several hours of physical activity in orbit, symptoms appeared, and thereafter both crewmen were compelled to limit head movements. Firm body contact with motionless surfaces helped alleviate symptoms. When crewmembers floated into unfamiliar body orientations in the cabin, inherent ambiguities in static visual orientation cues sometimes produced spatial reorientation episodes which were also provocative. Symptoms largely resembled those of other forms of prolonged motion sickness, superimposed upon other symptoms attributable to fluid shift. All 4 eventually used anti-motion sickness drugs. When they did, vomiting frequency was reduced. By the 4th day, symptoms subsided, and head accelerations again increased in magnitude and variability. Sickness intensity in orbit was not predicted by statistically concordant results of 6 acute preflight susceptibility tests. However, results from a longer duration preflight prism goggles test showed an apparent correlation. All subjects were asymptomatic making head movements in parabolic flight 4 days after the mission, but not 1 year later. Overall, results support the view that space sickness is a motion sickness.

African-specific variability in the acetylcholine muscarinic receptor M4: association with cocaine and heroin addiction.

PubMed

Levran, Orna; Randesi, Matthew; Peles, Einat; Correa da Rosa, Joel; Ott, Jurg; Rotrosen, John; Adelson, Miriam; Kreek, Mary Jeanne

2016-06-01

This study was designed to determine whether polymorphisms in acetylcholine receptors contribute to opioid dependence and/or cocaine dependence. The sample (n = 1860) was divided by drug and ancestry, and 55 polymorphisms (nine genes) were analyzed. Of the 20 SNPs that showed nominally significant associations, the association of the African-specific CHRM4 SNP rs2229163 (Asn417=) with cocaine dependence survived correction for multiple testing (Pcorrected = 0.047). CHRM4 is located in a region of strong linkage disequilibrium on chromosome 11 that includes genes associated with schizophrenia. CHRM4 SNP rs2229163 is in strong linkage disequilibrium with several African-specific SNPs in DGKZ and AMBRA1. Cholinergic receptors' variants may contribute to drug addiction and have a potential role as pharmacogenetic markers.

Reduced receptor aggregation and altered cytoskeleton in cultured myocytes after space-flight

NASA Technical Reports Server (NTRS)

Gruener, R.; Roberts, R.; Reitstetter, R.

1994-01-01

We carried out parallel experiments first on the slow clinostat and then in space-flight to examine the effects of altered gravity on the aggregation of the nicotinic acetylcholine receptors and the structure of the cytoskeleton in cultured Xenopus embryonic muscle cells. By examining the concordance between results from space flight and the clinostat, we tested whether the slow clinostat is a relevant simulation paradigm. Space-flown cells showed marked changes in the distribution and organization of actin filaments and had a reduced incidence of acetylcholine receptor aggregates at the site of contact with polystyrene beads. Similar effects were found after clinostat rotation. The sensitivity of synaptic receptor aggregation and cytoskeletal morphology suggests that in the microgravity of space cell behavior may be importantly altered.

Severe drug-induced repetitive behaviors and striatal overexpression of VAChT in ChAT-ChR2-EYFP BAC transgenic mice

PubMed Central

Lacey, Carolyn J.; Lee, Tyrone; Bowden, Hilary A.; Graybiel, Ann M.

2014-01-01

In drug users, drug-related cues alone can induce dopamine release in the dorsal striatum. Instructive cues activate inputs to the striatum from both dopaminergic and cholinergic neurons, which are thought to work together to support motor learning and motivated behaviors. Imbalances in these neuromodulatory influences can impair normal action selection and might thus contribute to pathologically repetitive and compulsive behaviors such as drug addiction. Dopamine and acetylcholine can have either antagonistic or synergistic effects on behavior, depending on the state of the animal and the receptor signaling systems at play. Semi-synchronized activation of cholinergic interneurons in the dorsal striatum drives dopamine release via presynaptic nicotinic acetylcholine receptors located on dopamine terminals. Nicotinic receptor blockade is known to diminish abnormal repetitive behaviors (stereotypies) induced by psychomotor stimulants. By contrast, blockade of postsynaptic acetylcholine muscarinic receptors in the dorsomedial striatum exacerbates drug-induced stereotypy, exemplifying how different acetylcholine receptors can also have opposing effects. Although acetylcholine release is known to be altered in animal models of drug addiction, predicting whether these changes will augment or diminish drug-induced behaviors thus remains a challenge. Here, we measured amphetamine-induced stereotypy in BAC transgenic mice that have been shown to overexpress the vesicular acetylcholine transporter (VAChT) with consequent increased acetylcholine release. We found that drug-induced stereotypies, consisting of confined sniffing and licking behaviors, were greatly increased in the transgenic mice relative to sibling controls, as was striatal VAChT protein. These findings suggest that VAChT-mediated increases in acetylcholine could be critical in exacerbating drug-induced stereotypic behaviors and promoting exaggerated behavioral fixity. PMID:24904300

The effect of brain death in rat steatotic and non-steatotic liver transplantation with previous ischemic preconditioning.

PubMed

Jiménez-Castro, Mónica B; Meroño, Noelia; Mendes-Braz, Mariana; Gracia-Sancho, Jordi; Martínez-Carreres, Laia; Cornide-Petronio, Maria Eugenia; Casillas-Ramirez, Araní; Rodés, Juan; Peralta, Carmen

2015-01-01

Most liver grafts undergoing transplantation derive from brain dead donors, which may also show hepatic steatosis, being both characteristic risk factors in liver transplantation. Ischemic preconditioning shows benefits when applied in non-brain dead clinical situations like hepatectomies, whereas it has been less promising in the transplantation from brain dead patients. This study examined how brain death affects preconditioned steatotic and non-steatotic liver grafts undergoing transplantation. Steatotic and non-steatotic grafts from non-brain dead and brain dead-donors were cold stored for 6h and then transplanted. After 2, 4, and 16 h of reperfusion, hepatic damage was analysed. In addition, two therapeutic strategies, ischemic preconditioning and/or acetylcholine pre-treatment, and their underlying mechanisms were characterized. Preconditioning benefits in non-brain dead donors were associated with nitric oxide and acetylcholine generation. In brain dead donors, preconditioning generated nitric oxide but did not promote acetylcholine upregulation, and this resulted in inflammation and damage. Acetylcholine treatment in brain dead donors, through PKC, increased antioxidants and reduced lipid peroxidation, nitrotyrosines and neutrophil accumulation, altogether protecting against damage. The combination of acetylcholine and preconditioning conferred stronger protection against damage, oxidative stress and neutrophil accumulation than acetylcholine treatment alone. These superior beneficial effects were due to a selective preconditioning-mediated generation of nitric oxide and regulation of PPAR and TLR4 pathways, which were not observed when acetylcholine was administered alone. Our findings propose the combination of acetylcholine+preconditioning as a feasible and highly protective strategy to reduce the adverse effects of brain death and to ultimately improve liver graft quality. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Synergistic effect between 5-HT4 receptor agonist and phosphodiesterase 4-inhibitor in releasing acetylcholine in pig gastric circular muscle in vitro.

PubMed

Lefebvre, Romain A; Van Colen, Inge; Pauwelyn, Vicky; De Maeyer, Joris H

2016-06-15

5-HT4 receptor agonists have a gastroprokinetic effect by facilitating acetylcholine release from cholinergic nerves innervating gastrointestinal smooth muscle. The role of phosphodiesterase (PDE) 4 in the signal transduction pathway of the 5-HT4 receptors located on the cholinergic neurons towards the circular muscle layer in pig stomach was investigated by analysis of acetylcholine release. Circular muscle strips were prepared from pig proximal stomach and tritium outflow, induced by electrical field stimulation, was studied as a marker for acetylcholine release after incubation with [(3)H]-choline. The PDE4-inhibitor roflumilast concentration-dependently (0.1-1µM) enhanced the facilitating effect of a submaximally effective concentration of the 5-HT4 receptor agonist prucalopride (0.01µM) on electrically induced acetylcholine release. Roflumilast (0.3µM) enhanced acetylcholine release per se but in the combined presence of roflumilast and prucalopride, acetylcholine release was enhanced more than the sum of the effect of the 2 compounds alone. The 5-HT4 receptor agonist velusetrag concentration-dependently (0.01-0.1µM) enhanced acetylcholine release; the effect of the minimally effective concentration (0.01µM) was significantly enhanced by 1µM of the PDE4-inhibitor rolipram, again to a level higher than the sum of the effect of the 2 compounds alone. The synergistic effect between 5-HT4 receptor agonists and PDE4-inhibitors demonstrates that the intracellular pathway of the 5-HT4 receptors located on cholinergic neurons towards pig gastric circular muscle is controlled by PDE4. Combining a 5-HT4 receptor agonist with a PDE4-inhibitor might thus enhance its gastroprokinetic effect. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of two doses of carbamylated allergoid extract of dust mite on nasal reactivity.

PubMed

Scalone, G; Compalati, E; Bruno, M E; Mistrello, G

2013-11-01

Background and Objective. Single SLIT studies with native allergen extracts support a dose-response effect for clinical and immunological outcomes. Conversely for carbamylated allergoids this dose-response effects is less evident, likely because the threshold for efficacy is more easily reached through the enhanced bioavailability of the extract consequent to the selective chemical modification. Thus this pilot study investigates the dose-response effect on nasal specific reactivity and safety of two unusual doses of carbamylated allergoid in patients mono-sensitized to house dust mites. Methods. A prospective open randomized study involved 6-65 year-old Italian patients with clinically relevant sensitization to house dust mites and positive response to nasal provocation challenge. Monomeric carbamylated allergoid was delivered once daily at the dose of 1000 AU or 2000 AU from June to September 2009, during the lowest level of mites exposure. Primary outcomes were the change of the threshold of allergen concentration for a positive nasal provocation test (NPT) before and after the treatment and the product safety. Secondary outcome was the change  in the mean percentage fall of peak nasal inspiratory flow (PNIF) following nasal challenge. Results. Thirty-four patients were enrolled. Fifteen in group 1 and 14 in group 2 concluded the study. After 12 weeks all patients treated in group 1 and all but one in group 2 showed an increase in the threshold dose provoking a positive NPT. Those with no symptoms onset with the highest dose delivered were 80% in group 1 and 78.6% in group 2 (p=0.92). From first to second challenge, the mean percentage fall of PNIF  was reduced with no statistical difference between groups (p=0.95), and with no difference between the final mean percentage falls (p=0.65). No serious adverse reactions occurred and the frequency of events, all mild, was similar in the two groups. Conclusions. Twelve weeks of carbamylated sublingual allergoid delivered at 1000AU or 2000AU once daily appear equally safe and show comparable effect in increasing  the threshold of allergen concentration for a positive nasal provocation test, confirming the apparent absence of a dose response effect for the used doses.

Detection of basal acetylcholine release in the microdialysis of rat frontal cortex by high-performance liquid chromatography using a horseradish peroxidase-osmium redox polymer electrode with pre-enzyme reactor.

PubMed

Kato, T; Liu, J K; Yamamoto, K; Osborne, P G; Niwa, O

1996-06-28

To determine the basal acetylcholine level in the dialysate of rat frontal cortex, a horseradish peroxidase-osmium redox polymer-modified glassy carbon electrode (HRP-GCE) was employed instead of the conventional platinum electrode used in high-performance liquid chromatography-electrochemical detection (HPLC-ED). In initial experiments, an oxidizable unknown compound interfered with the detection of basal acetylcholine release on HPLC-HRP-GCE. An immobilized peroxidase-choline oxidase precolumn (pre-reactor) was included in the HPLC system, to eliminate the interference from the unknown compound. This combination could detect less than 10 fmol of standard acetylcholine and basal acetylcholine levels in the dialysate from a conventional concentric design microdialysis probe, without the use of cholinesterase inhibitor, and may facilitate physiological investigation of cholinergic neuronal activity in the central nervous system.

Nonenzymatic all-solid-state coated wire electrode for acetylcholine determination in vitro.

PubMed

He, Cheng; Wang, Zhan; Wang, You; Hu, Ruifen; Li, Guang

2016-11-15

A nonenzymatic all-solid-state coated wire acetylcholine electrode was investigated. Poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate) (PEDOT/PSS) as conducting polymer was coated on one end of a gold wire (0.5mm in diameter). The acetylcholine selective membrane containing heptakis(2,3,6-tri-Ο-methyl)-β-cyclodextrin as an ionophore covered the conducting polymer layer. The electrode could work stably in a pH range of 6.5-8.5 and a temperature range of 15-40°C. It covered an acetylcholine concentration range of 10(-5)-10(-1)M with a slope of 54.04±1.70mV/decade, while detection limit was 5.69±1.06µM. The selectivity, dynamic response, reproducibility and stability were evaluated. The electrode could work properly in the rat brain homogenate to detect different concentrations of acetylcholine. Copyright © 2016 Elsevier B.V. All rights reserved.

Acetylcholine is released from taste cells, enhancing taste signalling

PubMed Central

Dando, Robin; Roper, Stephen D

2012-01-01

Acetylcholine (ACh), a candidate neurotransmitter that has been implicated in taste buds, elicits calcium mobilization in Receptor (Type II) taste cells. Using RT-PCR analysis and pharmacological interventions, we demonstrate that the muscarinic acetylcholine receptor M3 mediates these actions. Applying ACh enhanced both taste-evoked Ca2+ responses and taste-evoked afferent neurotransmitter (ATP) secretion from taste Receptor cells. Blocking muscarinic receptors depressed taste-evoked responses in Receptor cells, suggesting that ACh is normally released from taste cells during taste stimulation. ACh biosensors confirmed that, indeed, taste Receptor cells secrete acetylcholine during gustatory stimulation. Genetic deletion of muscarinic receptors resulted in significantly diminished ATP secretion from taste buds. The data demonstrate a new role for acetylcholine as a taste bud transmitter. Our results imply specifically that ACh is an autocrine transmitter secreted by taste Receptor cells during gustatory stimulation, enhancing taste-evoked responses and afferent transmitter secretion. PMID:22570381

Effect of chemical sympathectomy on the content of acetylcholine, choline and choline acetyltransferase activity in the cat spleen and iris.

PubMed

Consolo, S; Garattini, S; Ladinsky, H; Thoenen, H

1972-02-01

1. Acetylcholine and choline were measured in the spleens and irides of normal and 6-hydroxydopamine-treated cats. In addition, choline acetyltransferase activity was measured in the spleens.2. No acetylcholine or choline acetyltransferase activity were found in spleens of normal or treated cats. The choline content of normal spleens was 12.4 +/- 1.5 mug/g wet wt. (mean +/- S.E. of mean), which was not significantly altered by chemical sympathectomy.3. The acetylcholine and choline contents of the cat iris were 3.0 +/- 0.3 mug/g wet wt. and 7.7 +/- 0.9 mug/g wet wt., respectively. There was no difference in acetylcholine and choline concentrations between left and right or normal and sympathectomized irides.4. These results are discussed in relation to the question of a cholinergic link in post-ganglionic sympathetic transmission.

Reaching Out to Problem Anger: Assessing the Effectiveness of One-Day Cognitive Behavioural Workshops in a Community Setting in the UK.

PubMed

Illman, Nathan A; Brown, June S L

2016-09-01

Problem anger is frequently experienced by the general population and is known to cause significant problems for the individual and those around them. Whilst psychological treatments for problem anger are becoming increasingly established, this is still an under-researched area of mental health. We present an evaluation of a series of one-day anger management workshops for the public, targeting problem anger with a cognitive-behavioural approach. The main aim was to evaluate the effectiveness of a brief group-based anger intervention in terms of subjectively reported anger provocation levels and of depression and anxiety. Workshop participants completed a number of questionnaire measures at baseline before the intervention and at 1 month follow-up. The key questionnaires measured self-reported anger provocation levels (Novaco Anger Scale-Provocation Inventory), depressive symptomatology (PHQ-9) and symptoms of generalized anxiety (GAD-7). Change scores were analysed using repeated measures analyses. We found a significant reduction in anger provocation among workshop participants at 1 month follow-up (p = .03). Reductions in depression and anxiety were not statistically significant. We conclude that this brief psychoeducational anger intervention was effective in a small community sample and suggest future work should assess the effectiveness on similar brief interventions using a larger client group and examine outcomes on a broader range of anger measures.

Nanosensors for the Chemical Imaging of Acetylcholine Using Magnetic Resonance Imaging.

PubMed

Luo, Yi; Kim, Eric H; Flask, Chris A; Clark, Heather A

2018-06-06

A suite of imaging tools for detecting specific chemicals in the central nervous system could accelerate the understanding of neural signaling events critical to brain function and disease. Here, we introduce a class of nanoparticle sensors for the highly specific detection of acetylcholine in the living brain using magnetic resonance imaging. The nanosensor is composed of acetylcholine-catalyzing enzymes and pH-sensitive gadolinium contrast agents co-localized onto the surface of polymer nanoparticles, which leads to changes in T 1 relaxation rate (1/ T 1 ). The mechanism of the sensor involves the enzymatic hydrolysis of acetylcholine leading to a localized decrease in pH which is detected by the pH-sensitive gadolinium chelate. The concomitant change in 1/ T 1 in vitro measured a 20% increase from 0 to 10 μM acetylcholine concentration. The applicability of the nanosensors in vivo was demonstrated in the rat medial prefrontal cortex showing distinct changes in 1/ T 1 induced by pharmacological stimuli. The highly specific acetylcholine nanosensor we present here offers a promising strategy for detection of cholinergic neurotransmission and will facilitate our understanding of brain function through chemical imaging.

pH-dependent hydrolysis of acetylcholine: Consequences for non-neuronal acetylcholine.

PubMed

Wessler, Ignaz; Michel-Schmidt, Rosmarie; Kirkpatrick, Charles James

2015-11-01

Acetylcholine is inactivated by acetylcholinesterase and butyrylcholinesterase and thereby its cellular signalling is stopped. One distinguishing difference between the neuronal and non-neuronal cholinergic system is the high expression level of the esterase activity within the former and a considerably lower level within the latter system. Thus, any situation which limits the activity of both esterases will affect the non-neuronal cholinergic system to a much greater extent than the neuronal one. Both esterases are pH-dependent with an optimum at pH above 7, whereas at pH values below 6 particularly the specific acetylcholinesterase is more or less inactive. Thus, acetylcholine is prevented from hydrolysis at such low pH values. The pH of the surface of the human skin is around 5 and therefore non-neuronal acetylcholine released from keratinocytes can be detected in a non-invasive manner. Several clinical conditions like metabolic acidosis, inflammation, fracture-related haematomas, cardiac ischemia and malignant tumours are associated with local or systemic pH values below 7. Thus, the present article describes some consequences of an impaired inactivation of extracellular non-neuronal acetylcholine. Copyright © 2015 Elsevier B.V. All rights reserved.

Loss of Acetylcholine Signaling Reduces Cell Clearance Deficiencies in Caenorhabditis elegans.

PubMed

Pinto, Sérgio M; Almendinger, Johann; Cabello, Juan; Hengartner, Michael O

2016-01-01

The ability to eliminate undesired cells by apoptosis is a key mechanism to maintain organismal health and homeostasis. Failure to clear apoptotic cells efficiently can cause autoimmune diseases in mammals. Genetic studies in Caenorhabditis elegans have greatly helped to decipher the regulation of apoptotic cell clearance. In this study, we show that the loss of levamisole-sensitive acetylcholine receptor, but not of a typical neuronal acetylcholine receptor causes a reduction in the number of persistent cell corpses in worms suffering from an engulfment deficiency. This reduction is not caused by impaired or delayed cell death but rather by a partial restoration of the cell clearance capacity. Mutants in acetylcholine turn-over elicit a similar phenotype, implying that acetylcholine signaling is the process responsible for these observations. Surprisingly, tissue specific RNAi suggests that UNC-38, a major component of the levamisole-sensitive receptor, functions in the dying germ cell to influence engulfment efficiency. Animals with loss of acetylcholine receptor exhibit a higher fraction of cell corpses positive for the "eat-me" signal phosphatidylserine. Our results suggest that modulation by ion channels of ion flow across plasma membrane in dying cells can influence the dynamics of phosphatidylserine exposure and thus clearance efficiency.

Control of Insulin Secretion by Cholinergic Signaling in the Human Pancreatic Islet

PubMed Central

Molina, Judith; Rodriguez-Diaz, Rayner; Fachado, Alberto; Jacques-Silva, M. Caroline

2014-01-01

Acetylcholine regulates hormone secretion from the pancreatic islet and is thus crucial for glucose homeostasis. Little is known, however, about acetylcholine (cholinergic) signaling in the human islet. We recently reported that in the human islet, acetylcholine is primarily a paracrine signal released from α-cells rather than primarily a neural signal as in rodent islets. In this study, we demonstrate that the effects acetylcholine produces in the human islet are different and more complex than expected from studies conducted on cell lines and rodent islets. We found that endogenous acetylcholine not only stimulates the insulin-secreting β-cell via the muscarinic acetylcholine receptors M3 and M5, but also the somatostatin-secreting δ-cell via M1 receptors. Because somatostatin is a strong inhibitor of insulin secretion, we hypothesized that cholinergic input to the δ-cell indirectly regulates β-cell function. Indeed, when all muscarinic signaling was blocked, somatostatin secretion decreased and insulin secretion unexpectedly increased, suggesting a reduced inhibitory input to β-cells. Endogenous cholinergic signaling therefore provides direct stimulatory and indirect inhibitory input to β-cells to regulate insulin secretion from the human islet. PMID:24658304

The sympathetic postganglionic fibre and the block by bretylium; the block prevented by hexamethonium and imitated by mecamylamine

PubMed Central

Burn, J. H.; Gibbons, W. R.

1964-01-01

Acetylcholine, in the presence of atropine, has an action like that of sympathetic stimulation. When injected into the splenic artery it causes contraction of the spleen, but this action is blocked by hexamethonium; stimulation of the splenic nerves, however, is still effective. Thus hexamethonium distinguishes between sympathetic nerve stimulation and the action of acetylcholine. If bretylium is used instead of hexamethonium, there is no such distinction, for bretylium blocks the response to nerve stimulation as well as that to acetylcholine. It appeared that hexamethonium might block the action of acetylcholine by preventing its entry into the sympathetic fibre. Acetylcholine has some structural similarity to bretylium, since acetylcholine is a derivative of trimethylammonium and bretylium is a derivative of dimethylethylammonium. It has been found that hexamethonium, pentolinium and hemicholinium (HC-3), which are all bis-quaternary compounds, block the action of bretylium, presumably by preventing its entry into the fibre. Consistent with the view that ability to enter the fibre is important is the observation that mecamylamine and pempidine, which are ganglion-blocking agents, but not either mono- or bis-quaternary compounds, often abolish the response to stimulation of the sympathetic postganglionic fibre. PMID:14211685

NEURO-GUMORALE SUBSTANCES OF DOG BLOOD DURING ACUTE RADIATION SICKNESS. I. CHANGES IN BLOOD ACETYLCHOLINE AND CHOLINESTERASE SYSTEM (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuznetzova, N.E.

1963-01-01

Experiments carried out on 13 male dogs, 2 to 5 years old and weighing 10 to 20 kg, showed that in the initial stages of chroric radiation sickness the blood content of acetylcholine increased and the cholinesterase decreased. Moreove r, the increase in the acetylcholine level during the first 3 to 4 hrs proceeded at a greater rate than the cholinesterase decrease. Shifts in the enzyme system were more pronounced in dogs with greater resistance. However, during the recovery period acetylcholine and cholinesterase restoration took place at earlier periods in dogs with higher resistance. Not only was the cholinesterase activitymore » restored, but it increased to 1.5 to 2 times the initial level. The level of acetylcholine and cholinesterase was not restored in the blood of dogs during terminal periods. In dogs exposed to subacute doses, 300 r, enzyme normalization took place 29 to 41 days following exposure. Correlation of data on enzyme changes in single and chronic exposures indicated identical trends It was postulated that acetylcholine -cholinesterase participate in compensating reactions of organisms during radiation sickness. (R.V.J.)« less

Usefulness of In Vivo and In Vitro Diagnostic Tests in the Diagnosis of Hypersensitivity Reactions to Quinolones and in the Evaluation of Cross-Reactivity: A Comprehensive Study Including the Latest Quinolone Gemifloxacin

PubMed Central

Gelincik, Asli; Akdeniz, Nilgun; Aktas-Cetin, Esin; Olgac, Muge; Unal, Derya; Ertek, Belkis; Coskun, Raif; Colakoğlu, Bahattin; Deniz, Gunnur; Buyukozturk, Suna

2017-01-01

Purpose Reports evaluating diagnosis and cross reactivity of quinolone hypersensitivity have revealed contradictory results. Furthermore, there are no reports investigating the cross-reactivity between gemifloxacin (GFX) and the others. We aimed to detect the usefulness of diagnostic tests of hypersensitivity reactions to quinolones and to evaluate the cross reactivity between different quinolones including the latest quinolone GFX. Methods We studied 54 patients (mean age 42.31±10.39 years; 47 female) with 57 hypersensitivity reactions due to different quinolones and 10 nonatopic quinolone tolerable control subjects. A detailed clinical history, skin test (ST), and single-blind placebo-controlled drug provocation test (SBPCDPT), as well as basophil activation test (BAT) and lymphocyte transformation test (LTT) were performed with the culprit and alternative quinolones including ciprofloxacin (CFX), moxifloxacin (MFX), levofloxacin (LFX), ofloxacin (OFX), and GFX. Results The majority (75.9%) of the patients reported immediate type reactions to various quinolones. The most common culprit drug was CFX (52.6%) and the most common reaction type was urticaria (26.3%). A quarter of the patients (24.1%) reacted to SBPCDPTs, although their STs were negative; while false ST positivity was 3.5% and ST/SBPCDPTs concordance was only 1.8%. Both BAT and LTT were not found useful in quinolone hypersensitivity. Cross-reactivity was primarily observed between LFX and OFX (50.0%), whereas it was the least between MFX and the others, and in GFX hypersensitive patients the degree of cross-reactivity to the other quinolones was 16.7%. Conclusions These results suggest that STs, BAT, and LTT are not supportive in the diagnosis of a hypersensitivity reaction to quinolone as well as in the prediction of cross-reactivity. Drug provocation tests (DPTs) are necessary to identify both culprit and alternative quinolones. PMID:28497922

Gum Arabic as a Cause of Occupational Allergy

PubMed Central

Viinanen, Arja; Salokannel, Maija; Lammintausta, Kaija

2011-01-01

Background. Gum arabic is a potential sensitizer in food industry. Methods. We examined 11 candy factory workers referred to examinations due to respiratory and skin symptoms paying attention to exposure and sensitization to gum arabic. Skin tests, pulmonary function tests, and respiratory provocation tests were carried out as indicated by the symptoms and findings. Results. Occupational asthma, caused by gum arabic was diagnosed in 4/11 candy factory workers and two of them had also occupational contact urticaria and one had occupational rhinitis. One of them had oral symptoms associated with ingestion of products containing gum arabic. Conclusions. Airborne exposure to gum arabic may cause sensitization leading to allergic rhinitis, asthma, and urticaria. PMID:21747872

Occupational rhinitis in the Slovak Republic--a long-term retrospective study.

PubMed

Perečinský, Slavomir; Legáth, L'ubomír; Varga, Marek; Javorský, Martin; Bátora, Igor; Klimentová, Gabriela

2014-12-01

Allergic and non-allergic rhinitis ranks among the common occupational health problems. However, data on the incidence of occupational rhinitis are lacking, since comprehensive studies are rare. The study includes a group of patients in the Slovak Republic who were reported as having occupational rhinitis in the years 1990-2011. The following parameters were tracked in the investigated sample: age, gender, number of cases by individual years, occupations, causative factors and the length of exposure to the given agent. Possible progression of rhinitis to bronchial asthma was evaluated as well. The diagnostic algorithm was also analysed retrospectively, which included skin tests, the examination of specific IgE antibodies and nasal provocation tests. A total of 70 cases of occupational rhinitis were reported. The disease most often occurred in food industry workers (50% of cases). The most common aetiological factor was flour. Among other relatively common allergens were synthetic textile, wool, cotton and different types of moulds. Significant agents were also different chemical factors causing allergic and irritant rhinitis. The average length of exposure was 14.8 years. Exposure was shorter in men than in women (11 years vs. 16 years) (p = 0.04). Bronchial asthma as a comorbidity was diagnosed in 13 patients (19.7%). The critical diagnostic method on the basis of which the causal association between rhinitis and work environments was confirmed in 59% of cases was skin test; confirmation of the occupational cause using nasal provocation test was less frequent (18%). Food industry, textile industry and agriculture were the most risky occupational environments. Workers in these sectors require preventive intervention. In case of showing rhinitis symptoms it is necessary to confirm the occupational aetiology of the disease by the objective diagnostic methods. Since occupational rhinitis mostly precedes the occupational asthma, the elimination from the workplace is necessary.

Selective immediate responders to amoxicillin and clavulanic acid tolerate penicillin derivative administration after confirming the diagnosis.

PubMed

Blanca-Lopez, N; Perez-Alzate, D; Ruano, F; Garcimartin, M; de la Torre, V; Mayorga, C; Somoza, M L; Perkins, J; Blanca, M; Canto, M G; Torres, M J

2015-08-01

An increasing number of patients show immediate selective hypersensitivity reactions to clavulanic acid (CLV) and amoxicillin (AX), probably due to their increased prescription. The maintenance of this response should be established. To assess that the immediate hypersensitivity selective response to AX or to CLV is maintained after repeated administration of penicillin G (PG)/penicillin V (PV) and AX. Patients with proven immediate hypersensitivity to AX (Group A) or CLV (Group B) were included. Diagnosis was performed using skin tests with major and minor determinants of PG (PPL/MDM), AX and CLV and by drug provocation test (DPT) if required. Selectivity was established by confirming tolerance to PG/PV (Group A) and to PG/PV and AX (Group B). The maintenance of the selective response was verified by repeating DPT, 15 days after the initial investigation, with the same procedure. Of 51 patients, 78% belonged to Group A and 22% to Group B. Most had anaphylaxis. In Group A, 72% were skin test positive; 28% required DPT. In Group B, 63% were skin test positive; 37% required DPT. Only two AX-selective cases developed positive responses after re-provocation with PG/PV. No cases selective for CLV developed a positive response to PG, PV or AX. The selective response to AX appears consistent, and a response to penicillin determinants only develops in a minority of cases. For the case of CLV, the selective response appears not to be modified by exposure to penicillin determinants, meaning that patients with CLV allergy can take penicillin derivatives safely. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Uptake of /sup 3/H-choline and synthesis of /sup 3/H-acetylcholine by human penile corpus cavernosum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blanco, R.; Saenz de Tejada, I.; Azadzoi, K.

1986-03-05

The neuroeffectors which relax penile smooth muscle and lead to erection are unknown; physiological studies of human corpus cavernosum, in vitro, have suggested a significant role of cholinergic neurotransmission. To further characterize the importance of cholinergic nerves, biopsies of human corpus cavernosum were obtained at the time of penile prosthesis implantation. Tissues were incubated in /sup 3/H-choline (10/sup -5/M, 80 Ci/mmol) in oxygenated physiological salt solution at 37/sup 0/C, pH 7.4 for 1 hour. Radiolabelled compounds were extracted with perchloric acid (0.4 M) and acetylcholine and choline were separated by HPLC; /sup 14/C-acetylcholine was used as internal standard. /sup 3/H-cholinemore » was accumulated by the tissues (20 +/- 1.9 fmol/mg), and /sup 3/H-acetylcholine was synthesized (4.0 +/- 1.1 fmol/mg). In control experiments, heating of the tissue blocked synthesis of /sup 3/H-acetylcholine. Inhibition of high affinity choline transport by hemicholinium-3 (10/sup -5/M) diminished tissue accumulation of /sup 3/H-choline and significantly reduced the synthesis of /sup 3/H-acetylcholine (0.5 +/ 0.2 fmol/mg, p < 0.05). These results provide direct evidence of neuronal accumulation of choline and enzymatic conversion to acetylcholine in human corpus cavernosum. Taken together with the physiological studies, it can be concluded that cholinergic neurotransmission in human corpus cavernosum plays a role in penile erection.« less

Melatonin modulates rat myotube-acetylcholine receptors by inhibiting calmodulin.

PubMed

de Almeida-Paula, Lidiana Duarte; Costa-Lotufo, Leticia V; Silva Ferreira, Zulma; Monteiro, Amanda Elisa G; Isoldi, Mauro Cesar; Godinho, Rosely O; Markus, Regina P

2005-11-21

Melatonin, the pineal gland hormone, modulates alpha-bungarotoxin sensitive nicotinic acetylcholine receptors in sympathetic nerve terminals, cerebellum and chick retina imposing a diurnal variation in functional responses [Markus, R.P., Zago, W.M., Carneiro, R.C., 1996. Melatonin modulation of presynaptic nicotinic acetylcholine receptors in the rat vas deferens. J. Pharmacol. Exp. Ther. 279, 18-22; Markus, R.P., Santos, J.M., Zago, W., Reno, L.A., 2003. Melatonin nocturnal surge modulates nicotinic receptors and nicotine-induced [3HI] glutamate release in rat cerebellum slices. J. Pharmacol. Exp. Ther. 305, 525-530; Sampaio, L.F.S., Hamassaki-Britto, D.E., Markus, R.P., 2005. Influence of melatonin on the development of functional nicotinic acetylcholine receptors in cultured chick retinal cells. Braz. J. Med. Biol. Res. 38, 603-613]. Here we show that in rat myotubes forskolin and melatonin reduced the number of nicotinic acetylcholine receptors expressed in plasma membrane. In addition, these cells expressed melatonin MT1 receptors, which are known to be coupled to G(i)-protein. However, the pharmacological profile of melatonin analogs regarding the reduction in cyclic AMP accumulation and number of nicotinic acetylcholine receptors did not point to a mechanism mediated by activation of G(i)-protein coupled receptors. On the other hand, calmidazolium, a classical inhibitor of calmodulin, reduced in a similar manner both effects. Considering that one isoform of adenylyl cyclase present in rat myotubes is regulated by Ca2+/calmodulin, we propose that melatonin modulates the number of nicotinic acetylcholine receptors via reduction in cyclic AMP accumulation.

Ascorbic acid prevents vascular dysfunction induced by oral glucose load in healthy subjects.

PubMed

De Marchi, Sergio; Prior, Manlio; Rigoni, Anna; Zecchetto, Sara; Rulfo, Fanny; Arosio, Enrico

2012-01-01

To examine the effects of oral glucose load on forearm circulatory regulation before and after ascorbic acid administration in healthy subjects. Microcirculation study with laser Doppler was performed at the hand in basal conditions, after ischemia and after acetylcholine and nitroprusside; strain gauge plethysmography was performed at basal and after ischemia. The tests were repeated in the same sequence 2 hour after oral administration of glucose (75 g). The subjects were randomised for administration of ascorbic acid (1 g bid) or placebo (sodium bicarbonate 1 g bid) for 10 days. After that, the tests were repeated before and after a new oral glucose load. Blood pressure and heart rate were monitored. Macrocirculatory flux, pressure values and heart rate were unvaried throughout the study. The glucose load caused a reduction in the hyperemic peak flow with laser Doppler and plethysmography; it reduced flux recovery time and hyperemic curve area after ischemia; acetylcholine elicited a minor increase in flux with laser Doppler. The response to nitroprusside was unvaried after glucose load as compared to basal conditions. Treatment with ascorbic acid prevented the decrease in hyperemia after glucose, detected with laser Doppler and plethysmography. Ascorbic acid prevented the decreased response to acetylcholine after glucose, the response to nitroprusside was unaffected by ascorbic acid. Results after placebo were unvaried. Oral glucose load impairs endothelium dependent dilation and hyperaemia at microcirculation, probably via oxidative stress; ascorbic acid can prevent it. Copyright © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Tachykinin NK2 receptors predominantly mediate tachykinin-induced contractions in ovine trachea.

PubMed

Reynolds, A M; Reynolds, P; Holmes, M; Scicchitano, R

1998-01-12

In vitro studies were conducted to characterize the contractile effects of tachykinins in normal ovine trachea with a view in the future to compare tachykinin contractile responses in allergic tissue. Tracheal smooth muscle strips were prepared for in vitro studies of isometric contraction in response to cumulative addition of carbachol, acetylcholine, histamine, neuropeptide gamma, substance P, neurokinin A, neurokinin B, [Sar9, Met(O2)11]substance P, [Nle10]neurokinin A-(4-10), and [Succinyl-Asp6, Me-Phe8]substance P-(6-11) (senktide). The rank order of potency was neuropeptide gamma > carbachol > neurokinin A > or = [Nle10]neurokinin A-(4-10) > acetylcholine > or = histamine. Phosphoramidon enhanced the contractile response to neurokinin A and substance P, but not to neuropeptide gamma, [Sar9, Met(O2)11]substance P or senktide. Repeated cumulative concentration responses for acetylcholine, substance P, neurokinin A, [Sar9, Met(O2)11]substance P and histamine were also conducted to test for tachyphylaxis. No tachyphylaxis to acetylcholine, substance P, or neurokinin A was observed, however, [Sar9, Met(O2)11]substance P and histamine did exhibit tachyphylaxis. Atropine had no effect on tracheal contractions to neurokinin A and substance P, while [Sar9, Met(O2)11]substance P contractions were atropine sensitive. Pyrilamine did not affect substance P-induced tracheal smooth muscle contractions, indicating that the response to substance P was not mediated by histamine release. These results show that, in vitro, natural tachykinins induce tracheal smooth muscle contraction predominantly by a direct effect mediated by tachykinin NK2 receptors, and a small tachykinin NK1 receptor mediated cholinergic mechanism.

Susceptibility of Aedes aegypti, Culex quinquefasciatus Say, and Anopheles quadrimaculatus Say to 19 Pesticides with Different Modes of Action

DTIC Science & Technology

2008-01-01

imidacloprid , spinosad, diazinon, and carbaryl showed slightly lower activity than permethrin (20-fold). However, bifenazate showed very low activity...acetylcholinesterase inhibitor representing organophosphates (LD50 6.7 10 4 g/mg) imidacloprid , a nicotinic acetylcholine re- ceptor...inhibitors (Carbamates) 1A Spinosad Nicotinic acetylcholine receptor agonists 5 Imidacloprid Nicotinic acetylcholine receptor agonist/antagonists 4

Palmitic acid acutely inhibits acetylcholine- but not GLP-1-stimulated insulin secretion in mouse pancreatic islets

PubMed Central

Qin, Wei; Vinogradov, Sergei A.; Wilson, David F.; Matschinsky, Franz M.

2010-01-01

Fatty acids, acetylcholine, and GLP-1 enhance insulin secretion in a glucose-dependent manner. However, the interplay between glucose, fatty acids, and the neuroendocrine regulators of insulin secretion is not well understood. Therefore, we studied the acute effects of PA (alone or in combination with glucose, acetylcholine, or GLP-1) on isolated cultured mouse islets. Two different sets of experiments were designed. In one, a fixed concentration of 0.5 mM of PA bound to 0.15 mM BSA was used; in the other, a PA ramp from 0 to 0.5 mM was applied at a fixed albumin concentration of 0.15 mM so that the molar PA/BSA ratio changed within the physiological range. At a fixed concentration of 0.5 mM, PA markedly inhibited acetylcholine-stimulated insulin release, the rise of intracellular Ca2+, and enhancement of cAMP production but did not influence the effects of GLP-1 on these parameters of islet cell function. 2-ADB, an IP3 receptor inhibitor, reduced the effect of acetylcholine on insulin secretion and reversed the effect of PA on acetylcholine-stimulated insulin release. Islet perfusion for 35–40 min with 0.5 mM PA significantly reduced the calcium storage capacity of ER measured by the thapsigargin-induced Ca2+ release. Oxygen consumption due to low but not high glucose was reduced by PA. When a PA ramp from 0 to 0.5 mM was applied in the presence of 8 mM glucose, PA at concentrations as low as 50 μM significantly augmented glucose-stimulated insulin release and markedly reduced acetylcholine's effects on hormone secretion. We thus demonstrate that PA acutely reduces the total oxygen consumption response to glucose, glucose-dependent acetylcholine stimulation of insulin release, Ca2+, and cAMP metabolism, whereas GLP-1's actions on these parameters remain unaffected or potentiated. We speculate that acute emptying of the ER calcium by PA results in decreased glucose stimulation of respiration and acetylcholine potentiation of insulin secretion. PMID:20606076

Autoradiographic identification of acetylcholine in the rabbit retina

PubMed Central

1979-01-01

Rabbit retinas were studied in vitro under conditions known to maintain their physiological function. Retinas incubated in the presence of [3H]choline synthesized substantial amounts of both [3H]phosphorylcholine and [3H]acetylcholine. With time, [3H]phosphorylcholine proceeded into phospholipids, primarily phosphatidylcholine. Retinas pulse-labeled by a 15-min exposure to 0.3 microM [3H]choline were incubated for a subsequent hour under chase conditions designed either to retain newly synthesized acetylcholine within synapses or to promote its release. At the end of this time the two groups of retinas were found to contain equal amounts of radioactivity in the phospholipid pathway, but only the retinas incubated under the acetylcholine-protecting conditions contained [3H]acetylcholine. Freeze-dried, vacuum-embedded tissue from each retina was autoradiographed on dry emulsion. All retinas showed silver grains over the photoreceptor cells and faint labeling of all ganglion cells. In the retinas that contained [3H]acetylcholine, silver grains also accumulated densely over a few cells with the position of amacrine cells, over a subset of the cells of the ganglion cell layer, and in two bands over the inner plexiform layer. Fixation of the retina with aqueous osmium tetroxide retained only the radioactive compounds located in the photoreceptor and ganglion cells. Sections from freeze- dried tissue lost their water-soluble choline metabolites when exposed to water, and autoradiography of such sections again revealed radioactivity primarily in the photoreceptor and ganglion cells. Radioactive compounds extracted from the sections were found to faithfully reflect those present in the tissue before processing; analysis of the compounds eluted from sections microdissected along the outer plexiform layer showed [3H]acetylcholine to have been synthesized only by cells of the inner retina. Taken together, these results indicate that the photoreceptor and ganglion cells are distinguished by a rapid synthesis of choline-containing phospholipids, while acetylcholine synthesis is restricted to a few cells at both margins of the inner plexiform layer. They imply that the only neurons to release acetylcholine within the rabbit retina are a small group of probable amacrine cells. PMID:92476

Insecticidal and acetylcholine esterase inhibition activity of Apiaceae plant essential oils and their constituents against adults of German cockroach (Blattella germanica).

PubMed

Yeom, Hwa-Jeong; Kang, Jae Soon; Kim, Gil-Hah; Park, Il-Kwon

2012-07-25

We evaluated the insecticidal and acetylcholine esterase (AChE) inhibition activity of 11 Apiaceae plant essential oils and their constituents in adult male and female Blattella germanica. Of the 11 Apiaceae plant essential oils tested, dill (Anethum graveolens), carvi (Carum carvi), and cumin (Cuminum cyminum) demonstrated >90% fumigant toxicity against adult male German cockroaches at a concentration of 5 mg/filter paper. In a contact toxicity test, dill (Anethum graveolens), carvi (Carum carvi), cumin (Cuminum cyminum), and ajowan (Trachyspermum ammi) produced strong insecticidal activity against adult male and female German cockroaches. Among the test compounds, (S)-(+)-carvone, 1,8-cineole, trans-dihydrocarvone, cuminaldehyde, trans-anethole, p-cymene, and γ-terpinene demonstrated strong fumigant toxicity against adult male and female B. germanica. In a contact toxicity test, carveol, cuminaldehyde, (S)-(+)-carvone, trans-anethole, thymol, and p-cymene showed strong contact toxicity against adult male and female B. germanica. IC(50) values of α-pinene, carvacrol, and dihydrocarvone against female AChE were 0.28, 0.17, and 0.78 mg/mL, respectively. The toxicity of the blends of constituents identified in 4 active oils indicated that carvone, cuminaldehyde, and thymol were major contributors to the fumigant activity or contact toxicity of the artificial blend.

Repeated acetylcholine receptor antibody-concentrations and association to clinical myasthenia gravis development.

PubMed

Heldal, Anne Taraldsen; Eide, Geir Egil; Romi, Fredrik; Owe, Jone Furlund; Gilhus, Nils Erik

2014-01-01

We aimed to examine the longitudinal association between Myasthenia Gravis (MG) clinical severity and concentration of acetylcholine receptor (AChR)-antibodies to evaluate if AChR-antibody variations correlate to disease severity. A positive AChR-antibody test is specific for MG. All patients from western Norway who had two or more AChR- antibody tests in the period 1983-2013 were identified. The Myasthenia Gravis Foundation of America (MGFA) Clinical Classification was used to grade disease development. Multiple ordinal logistic regression analysis was used to estimate a possible predictive effect for AChR-antibody concentration on MGFA classification result. In 67 patients two or more AChR-antibody tests with a corresponding MGFA-score were performed, with a total of 309 tests. 56 patients were treated with immunosuppressive drugs and 11 by pyridostigmine only. There was a positive association between concentration of AChR-antibodies and longitudinal MGFA-score for the subgroup with immunosuppressive treatment, but not for those treated with pyridostigmine only. This association between AChR-antibody concentration and MGFA score declined with increasing time since onset (p = 0.005 for the interaction of group×time×concentration). For MG patients with immunosuppressive treatment, repeated AChR-antibody measurements give information about clinical development, and can therefore be of support in therapeutic decisions.

Provocative Endoscopy to Identify Bleeding Site in Upper Gastrointestinal Bleeding: A Novel Approach in Transarterial Embolization.

PubMed

Kamo, Minobu; Fuwa, Sokun; Fukuda, Katsuyuki; Fujita, Yoshiyuki; Kurihara, Yasuyuki

2016-07-01

This report describes a novel approach to endoscopically induce bleeding by removing a clot from the bleeding site during angiography for upper gastrointestinal (UGI) hemorrhage. This procedure enabled accurate identification of the bleeding site, allowing for successful targeted embolization despite a negative initial angiogram. Provocative endoscopy may be a feasible and useful option for angiography of obscure bleeding sites in patients with UGI arterial hemorrhage. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

Ankle pain and peroneal tendon pathology.

PubMed

Baumhauer, Judith F; Nawoczenski, Deborah A; DiGiovanni, Benedict F; Flemister, A Samuel

2004-01-01

Chronic ankle pain can be due to multiple causes. A thorough review of the patient's history with a physical examination concentrating on anatomic structures surrounding the ankle is imperative. The most common of causes have been presented. The addition of provocative testing and radiographic examinations can aid in elucidating the pathology. After treatment of the injury, attention to training technique, shoe and insert usage as well as individual gait abnormalities are integrated into global patient education to decrease the incidence of injury recurrence.

The Antinociceptive and Antiinflammatory Properties of 3-furan-2-yl-N-p-tolyl-acrylamide, a Positive Allosteric Modulator of α7 Nicotinic Acetylcholine Receptors in Mice

PubMed Central

Bagdas, Deniz; Targowska-Duda, Katarzyna M.; López, Jhon J.; Perez, Edwin G.; Arias, Hugo R.; Damaj, M. Imad

2016-01-01

BACKGROUND Positive allosteric modulators (PAMs) facilitate endogenous neurotransmission and/or enhance the efficacy of agonists without directly acting on the orthosteric binding sites. In this regard, selective α7 nicotinic acetylcholine receptor type II PAMs display antinociceptive activity in rodent chronic inflammatory and neuropathic pain models. This study investigates whether 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a new putative α7-selective type II PAM, attenuates experimental inflammatory and neuropathic pains in mice. METHODS We tested the activity of PAM-2 after intraperitoneal administration in 3 pain assays: the carrageenan-induced inflammatory pain, the complete Freund adjuvant induced inflammatory pain, and the chronic constriction injury–induced neuropathic pain in mice. We also tested whether PAM-2 enhanced the effects of the selective α7 agonist choline in the mouse carrageenan test given intrathecally. Because the experience of pain has both sensory and affective dimensions, we also evaluated the effects of PAM-2 on acetic acid–induced aversion by using the conditioned place aversion test. RESULTS We observed that systemic administration of PAM-2 significantly reversed mechanical allodynia and thermal hyperalgesia in inflammatory and neuropathic pain models in a dose- and time-dependent manner without motor impairment. In addition, by attenuating the paw edema in inflammatory models, PAM-2 showed antiinflammatory properties. The antinociceptive effect of PAM-2 was inhibited by the selective competitive antagonist methyllycaconitine, indicating that the effect is mediated by α7 nicotinic acetylcholine receptors. Furthermore, PAM-2 enhanced the antiallodynic and antiinflammatory effects of choline, a selective α7 agonist, in the mouse carrageenan test. PAM-2 was also effective in reducing acetic acid induced aversion in the conditioned place aversion assay. CONCLUSIONS These findings suggest that the administration of PAM-2, a new α7-selective type II PAM, reduces the neuropathic and inflammatory pain sensory and affective behaviors in the mouse. Thus, this drug may have therapeutic applications in the treatment and management of chronic pain. PMID:26280585

Enzyme-Controlled Nanodevice for Acetylcholine-Triggered Cargo Delivery Based on Janus Au-Mesoporous Silica Nanoparticles.

PubMed

Llopis-Lorente, Antoni; Díez, Paula; de la Torre, Cristina; Sánchez, Alfredo; Sancenón, Félix; Aznar, Elena; Marcos, María D; Martínez-Ruíz, Paloma; Martínez-Máñez, Ramón; Villalonga, Reynaldo

2017-03-28

This work reports a new gated nanodevice for acetylcholine-triggered cargo delivery. We prepared and characterized Janus Au-mesoporous silica nanoparticles functionalized with acetylcholinesterase on the Au face and with supramolecular β-cyclodextrin:benzimidazole inclusion complexes as caps on the mesoporous silica face. The nanodevice is able to selectively deliver the cargo in the presence of acetylcholine via enzyme-mediated acetylcholine hydrolysis, locally lowering the pH and opening the supramolecular gate. Given the key role played by ACh and its relation with Parkinson's disease and other nervous system diseases, we believe that these findings could help design new therapeutic strategies. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

M-cholinoreactivity of erythrocytes of non-pregnant and pregnant women evaluated by changes in the rate of erythrocyte agglutination under the influence of acetylcholine.

PubMed

Strelnikova, A I; Tsirkin, V I; Krysova, A V; Hlybova, S V; Dmitrieva, S L

2012-12-01

Acetylcholine (5.5×10(-10)-5.5×10(-6)M) accelerated erythrocyte agglutination in men, non-pregnant women in follicular phase of the menstrual cycle, and pregnant women in the first trimester. The effect was blocked with atropine (5.5×10(-6)M). Acetylcholine had no effect on the rate of erythrocyte agglutination in non-pregnant women in the luteal phase and pregnant women in the second and third trimesters, which coincided with the development of myometrium refractoriness to acetylcholine in pregnant women. The results indicate that erythrocytes can reflect M-cholinoreactivity of internal organs.

Nicotinic Cholinergic Receptor Binding Sites in the Brain: Regulation in vivo

NASA Astrophysics Data System (ADS)

Schwartz, Rochelle D.; Kellar, Kenneth J.

1983-04-01

Tritiated acetylcholine was used to measure binding sites with characteristics of nicotinic cholinergic receptors in rat brain. Regulation of the binding sites in vivo was examined by administering two drugs that stimulate nicotinic receptors directly or indirectly. After 10 days of exposure to the cholinesterase inhibitor diisopropyl fluorophosphate, binding of tritiated acetylcholine in the cerebral cortex was decreased. However, after repeated administration of nicotine for 10 days, binding of tritiated acetylcholine in the cortex was increased. Saturation analysis of tritiated acetylcholine binding in the cortices of rats treated with diisopropyl fluorophosphate or nicotine indicated that the number of binding sites decreased and increased, respectively, while the affinity of the sites was unaltered.

Effect of basal forebrain stimulation on extracellular acetylcholine release and blood flow in the olfactory bulb.

PubMed

Uchida, Sae; Kagitani, Fusako

2017-05-12

The olfactory bulb receives cholinergic basal forebrain input, as does the neocortex; however, the in vivo physiological functions regarding the release of extracellular acetylcholine and regulation of regional blood flow in the olfactory bulb are unclear. We used in vivo microdialysis to measure the extracellular acetylcholine levels in the olfactory bulb of urethane-anesthetized rats. Focal chemical stimulation by microinjection of L-glutamate into the horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain, which is the main source of cholinergic input to the olfactory bulb, increased extracellular acetylcholine release in the ipsilateral olfactory bulb. When the regional cerebral blood flow was measured using laser speckle contrast imaging, the focal chemical stimulation of the HDB did not significantly alter the blood flow in the olfactory bulb, while increases were observed in the neocortex. Our results suggest a functional difference between the olfactory bulb and neocortex regarding cerebral blood flow regulation through the release of acetylcholine by cholinergic basal forebrain input.

Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment.

PubMed

Lombardo, Sylvia; Maskos, Uwe

2015-09-01

Alzheimer's Disease (AD) is the major form of senile dementia, characterized by neuronal loss, extracellular deposits, and neurofibrillary tangles. It is accompanied by a loss of cholinergic tone, and acetylcholine (ACh) levels in the brain, which were hypothesized to be responsible for the cognitive decline observed in AD. Current medication is restricted to enhancing cholinergic signalling for symptomatic treatment of AD patients. The nicotinic acetylcholine receptor family (nAChR) and the muscarinic acetylcholine receptor family (mAChR) are the target of ACh in the brain. Both families of receptors are affected in AD. It was demonstrated that amyloid beta (Aβ) interacts with nAChRs. Here we discuss how Aβ activates or inhibits nAChRs, and how this interaction contributes to AD pathology. We will discuss the potential role of nAChRs as therapeutic targets. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. Copyright © 2014 Elsevier Ltd. All rights reserved.

Retinal co-mediator acetylcholine evokes muscarinic inhibition of recurrent excitation in frog tectum column.

PubMed

Baginskas, Armantas; Kuras, Antanas

2016-08-26

Acetylcholine receptors contribute to the control of neuronal and neuronal network activity from insects to humans. We have investigated the action of acetylcholine receptors in the optic tectum of Rana temporaria (common frog). Our previous studies have demonstrated that acetylcholine activates presynaptic nicotinic receptors, when released into the frog optic tectum as a co-mediator during firing of a single retinal ganglion cell, and causes: a) potentiation of retinotectal synaptic transmission, and b) facilitation of transition of the tectum column to a higher level of activity. In the present study we have shown that endogenous acetylcholine also activates muscarinic receptors, leading to a delayed inhibition of recurrent excitatory synaptic transmission in the tectum column. The delay of muscarinic inhibition was evaluated to be of ∼80ms, with an extent of inhibition of ∼2 times. The inhibition of the recurrent excitation determines transition of the tectum column back to its resting state, giving a functional sense for the inhibition. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

α7 Nicotinic Acetylcholine Receptor Signaling Inhibits Inflammasome Activation by Preventing Mitochondrial DNA Release

PubMed Central

Lu, Ben; Kwan, Kevin; Levine, Yaakov A; Olofsson, Peder S; Yang, Huan; Li, Jianhua; Joshi, Sonia; Wang, Haichao; Andersson, Ulf; Chavan, Sangeeta S; Tracey, Kevin J

2014-01-01

The mammalian immune system and the nervous system coevolved under the influence of cellular and environmental stress. Cellular stress is associated with changes in immunity and activation of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome, a key component of innate immunity. Here we show that α7 nicotinic acetylcholine receptor (α7 nAchR)-signaling inhibits inflammasome activation and prevents release of mitochondrial DNA, an NLRP3 ligand. Cholinergic receptor agonists or vagus nerve stimulation significantly inhibits inflammasome activation, whereas genetic deletion of α7 nAchR significantly enhances inflammasome activation. Acetylcholine accumulates in macrophage cytoplasm after adenosine triphosphate (ATP) stimulation in an α7 nAchR-independent manner. Acetylcholine significantly attenuated calcium or hydrogen oxide–induced mitochondrial damage and mitochondrial DNA release. Together, these findings reveal a novel neurotransmitter-mediated signaling pathway: acetylcholine translocates into the cytoplasm of immune cells during inflammation and inhibits NLRP3 inflammasome activation by preventing mitochondrial DNA release. PMID:24849809

Enzyme-linked DNA dendrimer nanosensors for acetylcholine

PubMed Central

Walsh, Ryan; Morales, Jennifer M.; Skipwith, Christopher G.; Ruckh, Timothy T.; Clark, Heather A.

2015-01-01

It is currently difficult to measure small dynamics of molecules in the brain with high spatial and temporal resolution while connecting them to the bigger picture of brain function. A step towards understanding the underlying neural networks of the brain is the ability to sense discrete changes of acetylcholine within a synapse. Here we show an efficient method for generating acetylcholine-detecting nanosensors based on DNA dendrimer scaffolds that incorporate butyrylcholinesterase and fluorescein in a nanoscale arrangement. These nanosensors are selective for acetylcholine and reversibly respond to levels of acetylcholine in the neurophysiological range. This DNA dendrimer architecture has the potential to overcome current obstacles to sensing in the synaptic environment, including the nanoscale size constraints of the synapse and the ability to quantify the spatio-temporal fluctuations of neurotransmitter release. By combining the control of nanosensor architecture with the strategic placement of fluorescent reporters and enzymes, this novel nanosensor platform can facilitate the development of new selective imaging tools for neuroscience. PMID:26442999

Enzyme-linked DNA dendrimer nanosensors for acetylcholine.

PubMed

Walsh, Ryan; Morales, Jennifer M; Skipwith, Christopher G; Ruckh, Timothy T; Clark, Heather A

2015-10-07

It is currently difficult to measure small dynamics of molecules in the brain with high spatial and temporal resolution while connecting them to the bigger picture of brain function. A step towards understanding the underlying neural networks of the brain is the ability to sense discrete changes of acetylcholine within a synapse. Here we show an efficient method for generating acetylcholine-detecting nanosensors based on DNA dendrimer scaffolds that incorporate butyrylcholinesterase and fluorescein in a nanoscale arrangement. These nanosensors are selective for acetylcholine and reversibly respond to levels of acetylcholine in the neurophysiological range. This DNA dendrimer architecture has the potential to overcome current obstacles to sensing in the synaptic environment, including the nanoscale size constraints of the synapse and the ability to quantify the spatio-temporal fluctuations of neurotransmitter release. By combining the control of nanosensor architecture with the strategic placement of fluorescent reporters and enzymes, this novel nanosensor platform can facilitate the development of new selective imaging tools for neuroscience.

Enzyme-linked DNA dendrimer nanosensors for acetylcholine

NASA Astrophysics Data System (ADS)

Walsh, Ryan; Morales, Jennifer M.; Skipwith, Christopher G.; Ruckh, Timothy T.; Clark, Heather A.

2015-10-01

It is currently difficult to measure small dynamics of molecules in the brain with high spatial and temporal resolution while connecting them to the bigger picture of brain function. A step towards understanding the underlying neural networks of the brain is the ability to sense discrete changes of acetylcholine within a synapse. Here we show an efficient method for generating acetylcholine-detecting nanosensors based on DNA dendrimer scaffolds that incorporate butyrylcholinesterase and fluorescein in a nanoscale arrangement. These nanosensors are selective for acetylcholine and reversibly respond to levels of acetylcholine in the neurophysiological range. This DNA dendrimer architecture has the potential to overcome current obstacles to sensing in the synaptic environment, including the nanoscale size constraints of the synapse and the ability to quantify the spatio-temporal fluctuations of neurotransmitter release. By combining the control of nanosensor architecture with the strategic placement of fluorescent reporters and enzymes, this novel nanosensor platform can facilitate the development of new selective imaging tools for neuroscience.

Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior

PubMed Central

Picciotto, Marina R.; Higley, Michael J.; Mineur, Yann S.

2012-01-01

Acetylcholine in the brain alters neuronal excitability, influences synaptic transmission, induces synaptic plasticity and coordinates the firing of groups of neurons. As a result, it changes the state of neuronal networks throughout the brain and modifies their response to internal and external inputs: the classical role of a neuromodulator. Here we identify actions of cholinergic signaling on cellular and synaptic properties of neurons in several brain areas and discuss the consequences of this signaling on behaviors related to drug abuse, attention, food intake, and affect. The diverse effects of acetylcholine depend on the site of release, the receptor subtypes, and the target neuronal population, however, a common theme is that acetylcholine potentiates behaviors that are adaptive to environmental stimuli and decreases responses to ongoing stimuli that do not require immediate action. The ability of acetylcholine to coordinate the response of neuronal networks in many brain areas makes cholinergic modulation an essential mechanism underlying complex behaviors. PMID:23040810

Effect of chemical sympathectomy on the content of acetylcholine, choline and choline acetyltransferase activity in the cat spleen and iris

PubMed Central

Consolo, S.; Garattini, S.; Ladinsky, H.; Thoenen, H.

1972-01-01

1. Acetylcholine and choline were measured in the spleens and irides of normal and 6-hydroxydopamine-treated cats. In addition, choline acetyltransferase activity was measured in the spleens. 2. No acetylcholine or choline acetyltransferase activity were found in spleens of normal or treated cats. The choline content of normal spleens was 12·4 ± 1·5 μg/g wet wt. (mean ± S.E. of mean), which was not significantly altered by chemical sympathectomy. 3. The acetylcholine and choline contents of the cat iris were 3·0 ± 0·3 μg/g wet wt. and 7·7 ± 0·9 μg/g wet wt., respectively. There was no difference in acetylcholine and choline concentrations between left and right or normal and sympathectomized irides. 4. These results are discussed in relation to the question of a cholinergic link in post-ganglionic sympathetic transmission. PMID:4335730

High outgroup entitativity can inhibit intergroup retribution.

PubMed

Newheiser, Anna-Kaisa; Dovidio, John F

2015-06-01

Understanding the psychological processes that are involved in the perpetuation and escalation of intergroup conflict remains an important goal for intergroup relations research. In the present research, we examined perceived outgroup entitativity as a potential determinant of intergroup hostility. In intergroup conflict situations, high-entitative outgroups are perceived as particularly deserving of retribution; however, high-entitative outgroups are also perceived as efficacious and capable of retaliating successfully, suggesting that people may inhibit hostility against high-entitative (vs. low-entitative) outgroups that are in a position to retaliate. We tested this prediction in two studies. In Study 1, we manipulated intergroup provocation and outgroup entitativity, and found that higher negative mood predicted greater aggression against a low-entitative provoker outgroup, but failed to predict aggression against a high-entitative provoker outgroup that was plausibly in a position to retaliate. In Study 2, we held provocation constant while manipulating outgroup entitativity and the possibility of retaliation by the outgroup, and found that people acted in a retributive manner against a high-entitative provoker outgroup only when the outgroup was not in a position to retaliate. Implications for intergroup conflict are discussed. © 2014 The British Psychological Society.

Neuromodulation of detrusor hyper-reflexia by functional magnetic stimulation of the sacral roots.

PubMed

Sheriff, M K; Shah, P J; Fowler, C; Mundy, A R; Craggs, M D

1996-07-01

To investigate the acute effects of functional magnetic stimulation (FMS) on detrusor hyper-reflexia using a multi-pulse magnetic stimulator. Seven male patients with established and intractable detrusor hyper-reflexia following spinal cord injury were studied. No patient was on medication and none had had previous surgery for detrusor hyper-reflexia. After optimization of magnetic stimulation of S2-S4 sacral anterior roots by recording toe flexor electromyograms, unstable detrusor activity was provoked during cystometry by rapid infusion of fluid into the bladder. The provocation test produced consistent and predictable detrusor hyper-reflexia. On some provocations, supramaximal FMS at 20 pulses/s for 5 s was applied at detrusor pressures which were > 15 cmH2O. Following FMS there was an obvious acute suppression of detrusor hyper-reflexia. There was a profound reduction in detrusor contraction, as assessed by the area under the curves of detrusor pressure with time. Functional magnetic stimulation applied over the sacrum can profoundly suppress detrusor hyper-reflexia in man. It may provide a non-invasive method of assessing patients for implantable electrical neuromodulation devices and as a therapeutic option in its own right.

Verbal ability and delinquency: testing the moderating role of psychopathic traits.

PubMed

Muñoz, Luna C; Frick, Paul J; Kimonis, Eva R; Aucoin, Katherine J

2008-04-01

Impaired verbal abilities are one of the most consistent risk factors for serious antisocial and delinquent behavior. However, individuals with psychopathic traits often show serious antisocial behavior, despite showing no impairment in their verbal abilities. Thus, the aim of the current study was to examine whether psychopathy moderates the relationship between verbal abilities and delinquent behavior in a sample of detained youth. The sample included 100 detained adolescent boys who were assessed on self-reported delinquent acts and psychopathic traits, as well as their age at first offense based on official records. Participants also completed a competitive computer task involving two levels of provocation, during which skin conductance was measured. A standard measure of receptive vocabulary was individually administered. As predicted, there was a significant interaction between callous-unemotional (CU) traits (a critical dimension of psychopathy) and verbal ability when predicting violent delinquency. Individuals who were high on CU traits with higher scores on the measure of verbal abilities reported the greatest violent delinquency. These individuals also showed the lowest level of skin conductance reactivity during the provocation task. The results suggest CU traits are an important moderator of the relation between verbal abilities and violent delinquency.

Self-regulatory failure and intimate partner violence perpetration.

PubMed

Finkel, Eli J; DeWall, C Nathan; Slotter, Erica B; Oaten, Megan; Foshee, Vangie A

2009-09-01

Five studies tested the hypothesis that self-regulatory failure is an important predictor of intimate partner violence (IPV) perpetration. Study 1 participants were far more likely to experience a violent impulse during conflictual interaction with their romantic partner than they were to enact a violent behavior, suggesting that self-regulatory processes help individuals refrain from perpetrating IPV when they experience a violent impulse. Study 2 participants high in dispositional self-control were less likely to perpetrate IPV, in both cross-sectional and residualized-lagged analyses, than were participants low in dispositional self-control. Study 3 participants verbalized more IPV-related cognitions if they responded immediately to partner provocations than if they responded after a 10-s delay. Study 4 participants whose self-regulatory resources were experimentally depleted were more violent in response to partner provocation (but not when unprovoked) than were nondepleted participants. Finally, Study 5 participants whose self-regulatory resources were experimentally bolstered via a 2-week training regimen exhibited less violent inclinations than did participants whose self-regulatory resources had not been bolstered. These findings hint at the power of incorporating self-regulation dynamics into predictive models of IPV perpetration. (c) 2009 APA, all rights reserved).

Repetitive transcranial magnetic stimulation modulates the impact of a negative mood induction

PubMed Central

Lacomblé, Lylis; Meyer, Thomas; Schutter, Dennis J.L.G.; Gielkens, Tom; Becker, Eni S.; Tendolkar, Indira; van Eijndhoven, Philip

2017-01-01

Abstract High frequency repetitive Transcranial Magnetic Stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been found to alleviate depressive symptoms. However, the mechanisms driving these effects are still poorly understood. In the current study, we tested the idea that this intervention protects against negative mood shifts following emotional provocation. We furthermore explored changes in EEG activity (frontal alpha asymmetry) and effects on attentional processing (emotional Stroop). To this end, 23 healthy individuals participated in two sessions separated by one week, whereby they once received 15 min of 10Hz rTMS stimulation (1500 pulses) at 110% of the individual motor threshold, and once sham stimulation. Then, negative mood was induced using sad movie clips. The results revealed a significantly stronger mood decline following rTMS compared to sham stimulation. No changes were observed in frontal alpha asymmetry and attentional processing. Our findings are at odds with the view that high frequency rTMS over the left DLPFC directly protects against the induction of negative mood, but rather suggest that it enhances the effects of emotional provocation. Possibly, in healthy young individuals, this stimulation protocol heightens susceptibility to mood induction procedures in general. PMID:28008080

[Automobile tyre colloidal particle induced allergic damage of respiratory system in traffic policemen and its allergenicity].

PubMed

Zhang, Yong-xing; Wei, Qing-yu; Wang, Juan; Qiao, Ting-hui; Bai, Hong-bing; Cai, Li-na

2007-06-01

To explore the damage of respiratory system in the traffic policemen induced by automobile tyre colloidal particle and its allergenicity. The respiratory system symptoms in 445 traffic policemen working outside their offices and 243 controls were investigated and their pulmonary ventilation function index such as FVC, FEV(1.0), MMF and V(50) were determined. The specific IgE antibody of automobile tyre colloidal particle of their serum was determined and the skin-prick test of automobile tyre colloidal particle antigen was performed. Sixty-six traffic policemen working outside their offices and 5 controls with the positive of IgE antibody among them were detected by nasal mucosa provocation test. Sixty-six traffic policemen working outside their offices with the positive of IgE antibody were determined by Terbutaline inhalation test. The positive rate of respiratory system symptoms of traffic policemen such as cough, stethocatharsis, short breath, nasal obstruction, sneeze and nose running was 38.02%, 27.03%, 20.00%, 23.08%, 27.47%, 32.09% and 34.95% respectively and significantly higher than those of the control with significant difference (P < 0.01) or (P < 0.05). The positive rate of specific IgE antibody of automobile tyre colloidal particle, skin- prick test and nasal mucosa provocation test was 14.51%, 23.73% and 54.55% respectively with significant difference (P < 0.01) and (P < 0.05). The percentage, the actual figure compared with the prediction figure, of the index of pulmonary ventilation function (FVC, FEV(1.0) MMF and V(50)) of traffic policemen were significantly lower than those of the control. Terbutaline inhalation test in 66 positive subjects of specific IgE antibody of automobile tyre colloidal particle was positive in 44 subjects, accounting for 9.67% in all policemen investigated. The automobile tyre colloidal particle is one of etiological factors that induce pulmonary ventilation function damage and could result in allergic asthma of traffic police.

Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming human beta cell function

PubMed Central

Rodriguez-Diaz, Rayner; Dando, Robin; Jacques-Silva, M. Caroline; Fachado, Alberto; Molina, Judith; Abdulreda, Midhat; Ricordi, Camillo; Roper, Stephen D.; Berggren, Per-Olof; Caicedo, Alejandro

2011-01-01

Acetylcholine is a neurotransmitter that plays a major role in the function of the insulin secreting pancreatic beta cell1,2. Parasympathetic innervation of the endocrine pancreas, the islets of Langerhans, has been shown to provide cholinergic input to the beta cell in several species1,3,4, but the role of autonomic innervation in human beta cell function is at present unclear. Here we show that, in contrast to mouse islets, cholinergic innervation of human islets is sparse. Instead, we find that the alpha cells of the human islet provide paracrine cholinergic input to surrounding endocrine cells. Human alpha cells express the vesicular acetylcholine transporter and release acetylcholine when stimulated with kainate or a lowering in glucose concentration. Acetylcholine secretion by alpha cells in turn sensitizes the beta cell response to increases in glucose concentration. Our results demonstrate that in human islets acetylcholine is a paracrine signal that primes the beta cell to respond optimally to subsequent increases in glucose concentration. We anticipate these results to revise models about neural input and cholinergic signaling in the endocrine pancreas. Cholinergic signaling within the islet represents a potential therapeutic target in diabetes5, highlighting the relevance of this advance to future drug development. PMID:21685896

Cholinergic modulation of cognitive processing: insights drawn from computational models

PubMed Central

Newman, Ehren L.; Gupta, Kishan; Climer, Jason R.; Monaghan, Caitlin K.; Hasselmo, Michael E.

2012-01-01

Acetylcholine plays an important role in cognitive function, as shown by pharmacological manipulations that impact working memory, attention, episodic memory, and spatial memory function. Acetylcholine also shows striking modulatory influences on the cellular physiology of hippocampal and cortical neurons. Modeling of neural circuits provides a framework for understanding how the cognitive functions may arise from the influence of acetylcholine on neural and network dynamics. We review the influences of cholinergic manipulations on behavioral performance in working memory, attention, episodic memory, and spatial memory tasks, the physiological effects of acetylcholine on neural and circuit dynamics, and the computational models that provide insight into the functional relationships between the physiology and behavior. Specifically, we discuss the important role of acetylcholine in governing mechanisms of active maintenance in working memory tasks and in regulating network dynamics important for effective processing of stimuli in attention and episodic memory tasks. We also propose that theta rhythm plays a crucial role as an intermediary between the physiological influences of acetylcholine and behavior in episodic and spatial memory tasks. We conclude with a synthesis of the existing modeling work and highlight future directions that are likely to be rewarding given the existing state of the literature for both empiricists and modelers. PMID:22707936

Protective effects of cultured and fermented ginseng extracts against scopolamine-induced memory loss in a mouse model.

PubMed

Han, Song-Hee; Kim, Sung-June; Yun, Young Won; Nam, Sang Yoon; Lee, Hu-Jang; Lee, Beom-Jun

2018-03-01

This study was performed to investigate the effect of a concentrate of fermented wild ginseng root culture (HLJG0701) on memory improvement in the scopolamine (SPL)-induced memory-deficient mouse model. Eight-week-old male ICR mice were used to evaluate the protective effect of HLJG0701 against the SPL-induced memory loss animal model. The Morris water maze test, which measures hippocampus-dependent learning ability, and the Y-maze test, a short-term memory assessment test, were performed and related markers were analyzed. HLJG0701-treated groups displayed significantly reduced acetylcholinesterase activity and increased acetylcholine level compared with the SPL-administered group (SPL-G) ( P <0.05). In the Y-maze test, the spontaneous alternation in al HLJG0711-treated groups was significantly increased compared with that in SPL-G ( P <0.05). In the Morris water maze test, the escape latency and time spent in the target quadrant in all HLJG0701-treated groups were significantly decreased and increased, respectively, compared with those in SPL-G ( P <0.05). In addition, the brain-derived neurotrophic factor level in groups treated with HLJG0701 300 and 600 mg/kg body weight was significantly increased compared with that in SPL-G ( P <0.05). These results suggest that the HLJG0701 may protect against memory loss by inhibiting acetylcholinesterase activity and preventing acetylcholine deficiency.

Cognitive impairment and olfactory panic from occupational exposure to VOCs.

PubMed

Reinhartz, Abe

2006-10-01

A Canadian government clerical worker in her early thirties developed frontal lobe dysfunction from inhalation of volatile organic compounds off-gassed during an office renovation. Pulmonary function, bronchial provocation, allergy testing, and a brain (SPECT) scan were performed. SPECT scanning showed frontotemporal hypoperfusion and neuropsychologic testing revealed deficits in verbal learning and poor organizational memory. A significant component of this worker's impairment was the development of "olfactory panic," a debilitating aversion to odor accompanied by symptoms of panic. The Ontario Workplace Safety and Insurance Appeals Tribunal granted entitlement for her cognitive difficulties and olfactory panic as a result of her toxic exposure.

Surface electromyography of myopotential oversensing provoked by simultaneous straining and leftward twisting in a patient with an implantable cardioverter defibrillator.

PubMed

Ajiro, Yoichi; Shiga, Tsuyoshi; Shoda, Morio; Hagiwara, Nobuhisa

2017-03-01

An important step in diagnosing myopotential oversensing is to confirm its reproducibility using specific provocation maneuvers. Although most maneuvers involve the co-contraction of many muscles, no attempt has been made to assess relevant muscle activities by electromyography. We describe a case with an implantable cardioverter defibrillator (ICD) whose myopotential oversensing was provoked by simultaneous straining and leftward twisting. Simultaneous recordings from real-time ICD telemetry and myopotentials of the rectus abdominis, oblique abdominis, and diaphragm on electromyography during the provocation maneuvers were conducted. It was shown that all three muscles contracted simultaneously during the provocation maneuvers; the diaphragm activity was the main source of noise oversensing, and the twist itself caused oversensing possibly due to the change in the position of the lead. In conclusion, the electromyographic assessment of relevant muscle activities may be useful in assessing each muscle's role and its contribution to myopotential oversensing, especially in a patient whose myopotential oversensing requires complex maneuvers to be provoked.

Philosophical Provocation: The Lifeblood of Clinical Ethics.

PubMed

McCullough, Laurence B

2017-02-01

The daily work of the clinical ethics teacher and clinical ethics consultant falls into the routine of classifying clinical cases by ethical type and proposing ethically justified alternatives for the professionally responsible management of a specific type of case. Settling too far into this routine creates the risk of philosophical inertia, which is not good either for the clinical ethicist or for the field of clinical ethics. The antidote to this philosophical inertia and resultant blinkered vision of clinical ethics is sustained, willing exposure to philosophical provocation. The papers in this clinical ethics issue of the Journal of Medicine and Philosophy provide just such philosophical provocation related to core topics in clinical ethics: the distinction between clinical practice and clinical research; telemedicine, or medicine at a distance; illness narratives; the concept of the placebo effect; and sex reassignment. © The Author 2017. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Experimental panic provocation in healthy man—a translational role in anti-panic drug development?

PubMed Central

Kellner, Michael

2011-01-01

Experimental neurochemical provocation of panic attacks in susceptible human subjects has considerably expanded our knowledge of the pathophysiology and psychopharmacology of panic disorder. Some panicogens also elicit short-lived panic-like states in healthy man. This offers the opportunity to assess the anti-panic action of drugs in proof-of-concept studies. However, from current data it is still unclear whether experimental panic in healthy man is a valid translational model. Most such studies in healthy volunteers have been performed using a cholecystokinin tetrapeptide (CCK-4) challenge. While CCK-4 panic was blocked by alprazolam pretreatment, escitalopram showed negative results in healthy man. Preliminary findings on novel investigational drugs and a few problematic results will be reviewed. Small sample sizes in many panic provocation studies, lack of dose-response aspects, and still-insufficient knowledge about the biological underpinning of experimental and spontaneous panic limit the interpretation of existing findings and should inspire further research. PMID:22275853

Role of ventrolateral orbital cortex muscarinic and nicotinic receptors in modulation of capsaicin-induced orofacial pain-related behaviors in rats.

PubMed

Tamaddonfard, Esmaeal; Erfanparast, Amir; Abbas Farshid, Amir; Delkhosh-Kasmaie, Fatmeh

2017-11-15

Acetylcholine, as a major neurotransmitter, mediates many brain functions such as pain. This study was aimed to investigate the effects of microinjection of muscarinic and nicotinic acetylcholine receptor antagonists and agonists into the ventrolateral orbital cortex (VLOC) on capsaicin-induced orofacial nociception and subsequent hyperalgesia. The right side of VLOC was surgically implanted with a guide cannula in anaesthetized rats. Orofacial pain-related behaviors were induced by subcutaneous injection of a capsaicin solution (1.5µg/20µl) into the left vibrissa pad. The time spent face rubbing with ipsilateral forepaw and general behavior were recorded for 10min, and then mechanical hyperalgesia was determined using von Frey filaments at 15, 30, 45 and 60min post-capsaicin injection. Alone intra-VLOC microinjection of atropine (a muscarinic acetylcholine receptor antagonist) and mecamylamine (a nicotinic acetylcholine receptor antagonist) at a similar dose of 200ng/site did not alter nocifensive behavior and hyperalgesia. Microinjection of oxotremorine (a muscarinic acetylcholine receptor agonist) at doses of 50 and 100ng/site and epibatidine (a nicotinic acetylcholine receptor agonist) at doses of 12.5, 25, 50 and 100ng/site into the VLOC suppressed pain-related behaviors. Prior microinjections of 200ng/site atropine and mecamylamine (200ng/site) prevented oxotremorine (100ng/site)-, and epibatidine (100ng/site)-induced antinociception, respectively. None of the above-mentioned chemicals changed general behavior. These results showed that the VLOC muscarinic and nicotinic acetylcholine receptors might be involved in modulation of orofacial nociception and hypersensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Nicotinic Acetylcholine Receptor (nAChR) Dependent Chorda Tympani Taste Nerve Responses to Nicotine, Ethanol and Acetylcholine.

PubMed

Ren, Zuo Jun; Mummalaneni, Shobha; Qian, Jie; Baumgarten, Clive M; DeSimone, John A; Lyall, Vijay

2015-01-01

Nicotine elicits bitter taste by activating TRPM5-dependent and TRPM5-independent but neuronal nAChR-dependent pathways. The nAChRs represent common targets at which acetylcholine, nicotine and ethanol functionally interact in the central nervous system. Here, we investigated if the nAChRs also represent a common pathway through which the bitter taste of nicotine, ethanol and acetylcholine is transduced. To this end, chorda tympani (CT) taste nerve responses were monitored in rats, wild-type mice and TRPM5 knockout (KO) mice following lingual stimulation with nicotine free base, ethanol, and acetylcholine, in the absence and presence of nAChR agonists and antagonists. The nAChR modulators: mecamylamine, dihydro-β-erythroidine, and CP-601932 (a partial agonist of the α3β4* nAChR), inhibited CT responses to nicotine, ethanol, and acetylcholine. CT responses to nicotine and ethanol were also inhibited by topical lingual application of 8-chlorophenylthio (CPT)-cAMP and loading taste cells with [Ca2+]i by topical lingual application of ionomycin + CaCl2. In contrast, CT responses to nicotine were enhanced when TRC [Ca2+]i was reduced by topical lingual application of BAPTA-AM. In patch-clamp experiments, only a subset of isolated rat fungiform taste cells exposed to nicotine responded with an increase in mecamylamine-sensitive inward currents. We conclude that nAChRs expressed in a subset of taste cells serve as common receptors for the detection of the TRPM5-independent bitter taste of nicotine, acetylcholine and ethanol.

Nicotinic Acetylcholine Receptor (nAChR) Dependent Chorda Tympani Taste Nerve Responses to Nicotine, Ethanol and Acetylcholine

PubMed Central

Ren, Zuo Jun; Mummalaneni, Shobha; Qian, Jie; Baumgarten, Clive M.; DeSimone, John A.; Lyall, Vijay

2015-01-01

Nicotine elicits bitter taste by activating TRPM5-dependent and TRPM5-independent but neuronal nAChR-dependent pathways. The nAChRs represent common targets at which acetylcholine, nicotine and ethanol functionally interact in the central nervous system. Here, we investigated if the nAChRs also represent a common pathway through which the bitter taste of nicotine, ethanol and acetylcholine is transduced. To this end, chorda tympani (CT) taste nerve responses were monitored in rats, wild-type mice and TRPM5 knockout (KO) mice following lingual stimulation with nicotine free base, ethanol, and acetylcholine, in the absence and presence of nAChR agonists and antagonists. The nAChR modulators: mecamylamine, dihydro-β-erythroidine, and CP-601932 (a partial agonist of the α3β4* nAChR), inhibited CT responses to nicotine, ethanol, and acetylcholine. CT responses to nicotine and ethanol were also inhibited by topical lingual application of 8-chlorophenylthio (CPT)-cAMP and loading taste cells with [Ca2+]i by topical lingual application of ionomycin + CaCl2. In contrast, CT responses to nicotine were enhanced when TRC [Ca2+]i was reduced by topical lingual application of BAPTA-AM. In patch-clamp experiments, only a subset of isolated rat fungiform taste cells exposed to nicotine responded with an increase in mecamylamine-sensitive inward currents. We conclude that nAChRs expressed in a subset of taste cells serve as common receptors for the detection of the TRPM5-independent bitter taste of nicotine, acetylcholine and ethanol. PMID:26039516

Metabolism of acetylcholine in human erythrocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, E.S.

1990-01-01

In order to examine the possible role of erythrocyte acetylcholinesterase in the maintenance of membrane phospholipid content and membrane fluidity, experiments were performed to monitor the activity of the enzyme and follow the fate of one of its hydrolytic products, choline. Intact human erythrocytes were incubated with acetylcholine (choline methyl-{sup 14}C). The incubation resulted in the hydrolysis of acetylcholine to acetate and choline; the reaction was catalyzed by membrane acetylcholinesterase. The studies demonstrate the further metabolism of choline. Experiments were carried out to determine rate of hydrolysis of acetylcholine, uptake of choline, identification of intracellular metabolites of choline, and identificationmore » of radiolabeled membrane components. Erythrocytes at a 25% hematocrit were incubated in an isoosmotic bicarbonate buffer pH 7.4, containing glucose, adenosine, streptomycin and penicillin with 0.3 {mu}Ci of acetylcholine (choline methyl-{sup 14}C), for 24 hours. Aliquots of the erythrocyte suspension were taken throughout for analysis. Erythrocytes were washed free of excess substrate, lysed, and the hemolysate was extracted for choline and its metabolites. Blank samples containing incubation buffer and radiolabeled acetylcholine only, and erythrocyte hemolysate extracts were analyzed for choline content, the difference between blank samples and hemolysate extracts was the amount of choline originating from acetylcholine and attributable to acetylcholinesterase activity. The conversion of choline to {sup 14}C-betaine is noted after several minutes of incubation; at 30 minutes, more than 80% of {sup 14}C-choline is taken up and after several hours, detectable levels of radiolabeled S-adenosylmethionine were present in the hemolysate extract.« less

Reduction of Mitochondria-Endoplasmic Reticulum Interactions by Acetylcholine Protects Human Umbilical Vein Endothelial Cells From Hypoxia/Reoxygenation Injury.

PubMed

He, Xi; Bi, Xue-Yuan; Lu, Xing-Zhu; Zhao, Ming; Yu, Xiao-Jiang; Sun, Lei; Xu, Man; Wier, W Gil; Zang, Wei-Jin

2015-07-01

We explored the role of endoplasmic reticulum (ER)-mitochondria Ca(2+) cross talk involving voltage-dependent anion channel-1 (VDAC1)/glucose-regulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex and mitofusin 2 in endothelial cells during hypoxia/reoxygenation (H/R), and investigated the protective effects of acetylcholine. Acetylcholine treatment during reoxygenation prevented intracellular and mitochondrial Ca(2+) increases and alleviated ER Ca(2+) depletion during H/R in human umbilical vein endothelial cells. Consequently, acetylcholine enhanced mitochondrial membrane potential and inhibited proapoptotic cascades, thereby reducing cell death and preserving endothelial ultrastructure. This effect was likely mediated by the type-3 muscarinic acetylcholine receptor and the phosphatidylinositol 3-kinase/Akt pathway. In addition, interactions among members of the VDAC1/glucose-regulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex were increased after H/R and were associated with mitochondrial Ca(2+) overload and cell death. Inhibition of the partner of the Ca(2+) channeling complex (VDAC1 siRNA) or a reduction in ER-mitochondria tethering (mitofusin 2 siRNA) prevented the increased protein interaction within the complex and reduced mitochondrial Ca(2+) accumulation and subsequent endothelial cell death after H/R. Intriguingly, acetylcholine could modulate ER-mitochondria Ca(2+) cross talk by inhibiting the VDAC1/glucose-regulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex and mitofusin 2 expression. Phosphatidylinositol 3-kinase siRNA diminished acetylcholine-mediated inhibition of mitochondrial Ca(2+) overload and VDAC1/glucose-regulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex formation induced by H/R. Our data suggest that ER-mitochondria interplay plays an important role in reperfusion injury in the endothelium and may be a novel molecular target for endothelial protection. Acetylcholine attenuates both intracellular and mitochondrial Ca(2+) overload and protects endothelial cells from H/R injury, presumably by disrupting the ER-mitochondria interaction. © 2015 American Heart Association, Inc.

In vivo neurochemical evidence that delta1-, delta2- and mu2-opioid receptors, but not mu1-opioid receptors, inhibit acetylcholine efflux in the nucleus accumbens of freely moving rats.

PubMed

Kiguchi, Yuri; Aono, Yuri; Watanabe, Yuriko; Yamamoto-Nemoto, Seiko; Shimizu, Kunihiko; Shimizu, Takehiko; Kosuge, Yasuhiro; Waddington, John L; Ishige, Kumiko; Ito, Yoshihisa; Saigusa, Tadashi

2016-10-15

Cholinergic neurons in the nucleus accumbens express delta- and mu-opioid receptors that are thought to inhibit neural activity. Delta- and mu-opioid receptors are divided into delta1- and delta2-opioid receptors and mu1- and mu2-opioid receptors, respectively. We analysed the roles of delta- and mu-opioid receptor subtypes in regulating accumbal acetylcholine efflux of freely moving rats using in vivo microdialysis. Other than naloxonazine, given intraperitoneally, delta- and mu-opioid receptor ligands were administered intracerebrally through the dialysis probe. Doses of these compounds indicate total amount (mol) over an infusion time of 30-60min. To monitor basal acetylcholine, a low concentration of physostigmine (50nM) was added to the perfusate. The delta1-opioid receptor agonist DPDPE (3 and 300pmol) and delta2-opioid receptor agonist deltorphin II (3 and 30pmol) decreased accumbal acetylcholine in a dose-related manner. DPDPE (300pmol)- and deltorphin II (3pmol)-induced reductions in acetylcholine were each inhibited by the delta1-opioid receptor antagonist BNTX (0.3pmol) and delta2-opioid receptor antagonist naltriben (15pmol), respectively. The mu-opioid receptor agonists endomorphin-1 and endomorphin-2 (6 and 30nmol) decreased acetylcholine in a dose-related manner. Endomorphin-1- and endomorphin-2 (30nmol)-induced reductions in acetylcholine were prevented by the mu-opioid receptor antagonist CTOP (3nmol). The mu1-opioid receptor antagonist naloxonazine (15mg/kg ip), which inhibits endomorphin-1 (15nmol)-induced accumbal dopamine efflux, did not alter endomorphin-1- or endomorphin-2 (30nmol)-induced reductions in acetylcholine efflux. This study provides in vivo evidence for delta1-, delta2- and mu2-opioid receptors, but not mu1-opioid receptors, that inhibit accumbal cholinergic neural activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of acute chlorpyrifos exposure on in vivo acetylcholine accumulation in rat striatum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karanth, Subramanya; Liu, Jing; Mirajkar, Nikita

2006-10-01

This study examined the acute effects of chlorpyrifos (CPF) on cholinesterase inhibition and acetylcholine levels in the striatum of freely moving rats using in vivo microdialysis. Adult, male Sprague-Dawley rats were treated with vehicle (peanut oil, 2 ml/kg) or CPF (84, 156 or 279 mg/kg, sc) and functional signs of toxicity, body weight and motor activity recorded. Microdialysis was conducted at 1, 4 and 7 days after CPF exposure for measurement of acetylcholine levels in striatum. Rats were then sacrificed and the contralateral striatum and diaphragm were collected for biochemical measurements. Few overt signs of cholinergic toxicity were noted inmore » any rats. Body weight gain was significantly affected in the high-dose (279 mg/kg) group only, while motor activity (nocturnal rearing) was significantly reduced in all CPF-treated groups at one day (84 mg/kg) or from 1-4 days (156 and 279 mg/kg) after dosing. Cholinesterase activities in both diaphragm and striatum were markedly inhibited (50-92%) in a time-dependent manner, but there were relatively minimal dose-related changes. In contrast, time- and dose-dependent changes in striatal acetylcholine levels were noted, with significantly higher levels noted in the high-dose group compared to other groups. Maximal increases in striatal acetylcholine levels were observed at 4-7 days after dosing (84 mg/kg, 7-9-fold; 156 mg/kg, 10-13-fold; 279 mg/kg, 35-57-fold). Substantially higher acetylcholine levels were noted when an exogenous cholinesterase inhibitor was included in the perfusion buffer, but CPF treatment-related differences were substantially lower in magnitude under those conditions. The results suggest that marked differences in acetylcholine accumulation can occur with dosages of CPF eliciting relatively similar degrees of cholinesterase inhibition. Furthermore, the minimal expression of classic signs of cholinergic toxicity in the presence of extensive brain acetylcholine accumulation suggests that some compensatory process(es) downstream from synaptic neurotransmitter accumulation limits the expression of toxicity following acute CPF exposure.« less

Acetylcholine-Like Molecular Arrangement in Psychomimetic Anticholinergic Drugs

PubMed Central

Maayani, Saul; Weinstein, Harel; Cohen, Sasson; Sokolovsky, Mordechai

1973-01-01

A study of the relation between the psychotropic activity and the antagonism to acetylcholine observed for some heterocyclic amino esters and compounds of the phencyclidine series suggests some common molecular structural requirements for their properties. Criteria obtained from quantum mechanical calculations of acetylcholine-like molecules indicate that their molecular reactivity with the cholinergic receptor site follows a certain dynamic interaction pattern. This pattern suggests a certain molecular arrangement essential for the interaction, which is based on the electronic properties of the molecules and therefore remains valid for the evaluation of compounds which lack any apparent similarity to acetylcholine. This type of molecular arrangement is shown to be shared by both activators and inhibitors of the acetylcholine receptor discussed here, thus supporting the hypothesis of their binding to a common receptor. The differences in biological activity are attributed to the effect of molecular structural factors which are not commonly included in the molecular arrangement based on the active groups of acetylcholine. The role of such factors is revealed by a study of the observed differences in the cholinergic and psychomimetic activities of related pairs of isomers and enantiomers of the molecules investigated. Structural factors which interfere with the conformational changes occurring in the receptor protein induced by an activator are characterized through differences obtained by the comparative investigation of the activities of the agonist acetate and the antagonist benzilate amino esters of quinuclidine, tropine, and pseudotropine. The same factors are shown in studies of the phencyclidine series to contribute to the antagonism to acetylcholine activity that is closely related to the psychomimetic activity of these drugs in the central nervous system. Similarly, phencyclidine derivatives in which the characteristic acetylcholine-like molecular arrangement is modified by various substitutions are shown to loose both anticholinergic and psychotropic behavior. This close correlation is supported by the identification of molecular regions which will generate the proper molecular arrangement in local anesthetics and morphine, compounds which are known to be involved in cholinergic mechanisms. Images PMID:4522291

Susceptibility of Bemisia tabaci MEAM1 (Hemiptera: Aleyrodidae) to imidacloprid, thiamethoxam, dinotefuran and flupyradifurone in south Florida

USDA-ARS?s Scientific Manuscript database

Populations of Bemisa tabaci Middle East Asia Minor 1 (MEAM 1) were established from nineteen locations in south Florida, primarily from commercial tomato fields, and were tested using a cotton leaf petiole systemic uptake method for susceptibility to the nicotinic acetylcholine agonist insecticides...

Anagyrine desensitization of peripheral nicotinic acetylcholine receptors. A potential biomarker of quinolizidine alkaloid teratogenesis in cattle.

USDA-ARS?s Scientific Manuscript database

Anagyrine, a teratogenic quinolizidine alkaloid found in certain Lupinus spp., has been proposed to undergo metabolism by pregnant cattle to a piperidine alkaloid which acts inhibit fetal movement, the putative mechanism behind crooked calf syndrome. The objective of this study was to test the hypot...

Rapid and selective detection of botulinum neurotoxin serotypes-A and –B with a single immunochromatographic test strip

USDA-ARS?s Scientific Manuscript database

Seven, antigenically distinct botulinum neurotoxins (BoNT) are produced by the bacterium Clostridium botulinum and classified into serotypes designated A-G. In animals these potent toxin acts to inhibit acetylcholine release, resulting in paralysis and death. BoNT/A and /B, together represent >80% o...

The non-competitive blockade of GABAA receptors by an aqueous extract of water hemlock (Cicuta douglassi) tubers

USDA-ARS?s Scientific Manuscript database

Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement from the desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChR). In this study, we tested the hypothesis that the piperidine alkaloid anabaseine a 1,2-dehydropiperidine and anabasin...

Networks of phobic fear: Functional connectivity shifts in two subtypes of specific phobia.

PubMed

Stefanescu, Maria R; Endres, Ralph J; Hilbert, Kevin; Wittchen, Hans-Ulrich; Lueken, Ulrike

2018-01-01

Anxiety disorders can be conceptualized by an abnormal interplay of emotion-processing brain circuits; however, knowledge of brain connectivity measures in specific phobia is still limited. To explore functional interactions within selected fear-circuitry structures (anterior cingulate cortex (ACC), amygdala, insula), we re-examined three task-based fMRI studies using a symptom provocation approach (n=94 subjects in total) on two different phobia subtypes (animal subtype as represented by snake phobia (SP) and blood-injection-injury subtype as represented by dental phobia (DP)), and a non-phobic healthy control group (HC). Functional connectivity (FC) analyses detected a negative coupling between the amygdala and the ACC in HC for both classes of phobic stimuli, while SP and DP lacked this inhibitory relationship during visual stimulus presentation. However, a negative FC between the insula and the amygdala was observed in DP during visual symptom provocation, which reversed to a positive FC under auditory symptom provocation pointing to effects depending on stimulus modality in DP. SP showed significantly higher FC towards snake-anxiety eliciting stimuli than HC on an average measure of FC, while DP showed a similar pattern under auditory stimulation only. These findings altogether indicate FC shifts during symptom provocation in specific phobia possibly reflecting impaired emotion regulation processes within fear-circuitry networks. FC hence could represent a prime target for neuroscience-informed augmentation strategies when treating pathological forms of fear. Copyright © 2017 Elsevier B.V. All rights reserved.

Trait aggressiveness modulates neurophysiological correlates of laboratory-induced reactive aggression in humans.

PubMed

Krämer, Ulrike M; Büttner, Sarah; Roth, Gerhard; Münte, Thomas F

2008-08-01

Reactive aggression following provocation is a frequent form of human social behavior. The neural basis of reactive aggression, especially its control, remains poorly understood, however. We conducted an event-related potential (ERP) study using a competitive reaction time task that elicits aggression through provocation. Participants were selected from a larger sample because of extreme scores in trait aggressiveness, yielding high and low trait aggressive groups. As each trial in the task is separated into a decision phase, during which the punishment level for the opponent is set, and an outcome phase, during which the punishment is applied or received, we were able to disentangle provocation-related and evaluation-related modulations of the ERPs during the aggressive interaction. Specifically, we observed an enhanced frontal negativity during the decision phase under high provocation that was positively correlated with the participants' ability to refrain from retaliation. This held true for high trait aggressive participants only, pointing to a higher need for inhibitory and control processes in these people when provoked. During the outcome phase, we detected a mediofrontal negativity in loss compared to win trials, resembling previous ERP findings to negative feedback stimuli, which have been linked to the evaluation of an outcome's valence. This mediofrontal negativity was differentially pronounced in aggressive and nonaggressive participants: Nonaggressive participants showed only a slightly smaller mediofrontal negativity in win than in loss trials, suggesting that for them punishing the opponent had a similar negative valence as being punished.

Lambert-Eaton syndrome

MedlinePlus

... unable to release enough of a chemical called acetylcholine. This chemical transmits impulses between nerves and muscles. ... given alone) Drugs that increase the release of acetylcholine from nerve cells

An ab initio study of the conformational energy map of acetylcholine

NASA Astrophysics Data System (ADS)

Segall, M. D.; Payne, M. C.; Boyes, R. N.

An ab initio density functional theory study is reported of the conformational energy map of acetylcholine, with respect to the two central dihedral angles of the molecule. The acetylcholine molecule pays a central role in neurotransmission and has been studied widely using semi-empirical computational modelling. The ab initio results are compared with a number of previous investigations and with experiment. The ab initio data indicate that the most stable conformation of acetylcholine is the trans , gauche arrangement of the central dihedral angles. Furthermore, Mulliken population analysis of the electronic structure of the molecule in this conformation indicates that the positive charge of the molecule is spread over the exterior of the cationic head of the molecule.

Acetylcholine Mediates a Slow Synaptic Potential in Hippocampal Pyramidal Cells

NASA Astrophysics Data System (ADS)

Cole, A. E.; Nicoll, R. A.

1983-09-01

The hippocampal slice preparation was used to study the role of acetylcholine as a synaptic transmitter. Bath-applied acetylcholine had three actions on pyramidal cells: (i) depolarization associated with increased input resistance, (ii) blockade of calcium-activated potassium responses, and (iii) blockade of accommodation of cell discharge. All these actions were reversed by the muscarinic antagonist atropine. Stimulation of sites in the slice known to contain cholinergic fibers mimicked all the actions. Furthermore, these evoked synaptic responses were enhanced by the cholinesterase inhibitor eserine and were blocked by atropine. These findings provide electrophysiological support for the role of acetylcholine as a synaptic transmitter in the brain and demonstrate that nonclassical synaptic responses involving the blockade of membrane conductances exist in the brain.

Natural rubber latex skin testing reagents: safety and diagnostic accuracy of nonammoniated latex, ammoniated latex, and latex rubber glove extracts.

PubMed

Hamilton, R G; Adkinson, N F

1996-11-01

Nonammoniated latex, ammoniated latex, and rubber glove extracts are the only sources of natural rubber (Hevea brasiliensis) latex that have potential for use as skin testing reagents in the diagnosis of latex allergy. Their diagnostic sensitivity and specificity as skin test reagents are unknown. We conducted a phase 1/2 clinical study to examine the safety and diagnostic accuracy (sensitivity and specificity) of nonammoniated latex, ammoniated latex, and rubber glove extracts as skin test extracts to identify the most efficacious source material for future skin test reagent development. Twenty-four adults not allergic to latex, 19 adults with hand dermatitis or pruritus, and 59 adults with a latex allergy were identified by clinical history. All provided blood and then received puncture skin tests and intradermal skin tests with nonammoniated latex, ammoniated latex, and rubber glove extracts from Malaysian H. brasiliensis latex by use of sequential titration. A glove provocation test and IgE anti-latex RAST were used to clarify positive history-negative skin test response and negative history-positive skin test response mismatches. All three extracts were biologically safe and sterile. After normalization to 1 mg/ml of total protein, all three extracts produced equivalent diagnostic sensitivity and specificity in puncture skin tests and intradermal skin tests at various extract concentrations. Optimal diagnostic accuracy was safely achieved at 100 micrograms/ml for intradermal skin tests (e.g., nonammoniated latex: puncture skin test sensitivity 96%, specificity 100%; intradermal skin test sensitivity 93%, specificity 96%). The presence of IgE antibody in skin was highly correlated with IgE anti-latex in serum (nonammoniated latex: r = 0.98, p < 0.001; ammoniated latex: r = 0.94, p < 0.001; rubber glove extract: r = 0.96, p < 0.001). All five available subjects with a positive history, negative skin test response, and absence of IgE antibody in serum had a negative glove provocation test response, indicating no clinical evidence of latex allergy. No systemic or large local allergic reactions were observed with puncture skin tests or intradermal skin tests. Equivalent diagnostic sensitivity and specificity were observed with the nonammoniated latex, ammoniated latex, and rubber glove extract skin test reagents after normalization for total protein; nonammoniated latex may be considered the reagent of choice on the basis of practical quality control and reproducibility considerations.

Inhibition of chemically induced inflammation and pain by orally and topically administered leaf extract of Manihot esculenta Crantz in rodents.

PubMed

Adeyemi, Olufunmilayo O; Yemitan, Omoniyi K; Afolabi, Lateef

2008-09-02

The aqueous leaf extract of Manihot esculenta Crantz (MELE) is being used orally and topically in traditional African medicine for the treatment of inflammation and pain, and claimed to be safe. The anti-inflammatory effects of MELE (100-400 mg/kg, p.o. or 1-4%, w/w in petroleum jelly, topically) were tested against carrageenan-induced paw oedema in rats as well as against xylene-induced ear oedema in mice. The analgesic effect of MELE (100-400 mg/kg, p.o. or 1-4%, w/w in petroleum jelly, topically) was tested against acetic acid-induced (20 microl, 0.6%, v/v in normal saline, i.p.) and acetylcholine-induced (8.3 mg/kg, i.p.) mouse writhing models. At 100-400 mg/kg, p.o. and 1-4% (w/w), topically, MELE produced significant inhibitions of carrageenan-induced rat paw oedema and xylene-induced ear swelling in mice. Effects produced by MELE were significantly higher than those produced by indomethacin (10 mg/kg, s.c. or 1%, w/w in petroleum jelly) in the anti-inflammatory models. For the analgesic effect, MELE (100-400 mg/kg, orally) and (1-4%, w/w, topically), like aspirin (100 mg/kg, i.p.) exhibited significant (P<0.05) inhibition of acetic acid- and acetylcholine-induced mouse writhing tests, compared to untreated control. Effects produced by MELE were significantly lower than those produced by aspirin (100 mg/kg, i.p.) in the analgesic models, except for the topically administered extract on acetylcholine-induced pain. Acute oral administration up to 10 g/kg did not cause death within 14 days, but mortalities were produced in i.p. administered extract with LD(50) of 2.5+/-0.3 g/kg. Based on these, the extract may contain orally safe, topically and orally effective anti-inflammatory and analgesic principles, which justify its use in traditional African medicine.

Correlation of skin test results and specific immunoglobulin E blood levels with nasal provocation testing for house-dust mite allergies.

PubMed

Haxel, Boris R; Huppertz, Tilman; Boessert, Patrick; Bast, Florian; Fruth, Kai

2016-01-01

Allergen-specific immunotherapy for house-dust mite (HDM) allergies is associated with lower success rates when compared with similar treatments for other inhalant allergens, such as grass or birch. One reason might be the greater difficulty in diagnosing patients with assumed HDM allergies because symptoms occur perennially and may differ from those of a conventional allergic rhinitis. The aim of the study was to compare the different methods of diagnosis in patients with assumed HDM allergy. We performed a retrospective analysis of nasal provocation tests (NPT) from patients (n = 161) evaluated for Dermatophagoides pteronyssinus (n = 127) and Dermatophagoides farinae (n = 104) allergies, and compared the results with other allergen testing methods (skin-prick test [SPT], intracutaneous test, and allergen specific immunoglobulin E levels [sIgE] to detect sensitization). Receiver operating characteristic curves were used for the analyses and the areas under the curve were calculated. For D. pteronyssinus and D. farinae, 86 and 70 complete data files, respectively, were available. For both tested HDMs, the results of the receiver operating characteristic curves showed a significant correlation for SPT and sIgE, with the results of the NPT (area under the curve, 0.742 to 0.763) but not for the intracutaneous test. In patients with a positive SPT (≥3 mm), an allergy was confirmed by the NPT in 69% of cases for D. pteronyssinus and 71% for D. farinae. A positive sIgE result (ImmunoCAP class of ≥2) was verified by the NPT in 69% of cases (D. pteronyssinus) and 70% (D. farinae). The predictability value for a positive NPT result is best for SPT and sIgE. Nevertheless, even if the results of both test systems are combined, the positive predictive value that was achieved was only 0.77 for D. pteronyssinus and 0.69 for D. farinae. Therefore, in patients eligible for immunotherapy for HDM, an NPT should be performed before the start of the therapy to verify a clinically relevant allergy.

Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects

PubMed Central

2013-01-01

Background Alzheimer’s disease (AD) as neurodegenerative disorder, is the most common form of dementia accounting for about 50-60% of the overall cases of dementia among persons over 65 years of age. Low acetylcholine (ACh) concentration in hippocampus and cortex areas of the brain is one of the main reasons for this disease. In recent years, acetylcholinesterase (AChE) inhibitors like donepezil with prevention of acetylcholine hydrolysis can enhance the duration of action of acetylcholine in synaptic cleft and improve the dementia associated with Alzheimer’s disease. Results Design, synthesis and assessment of anticholinesterase activity of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives showed prepared compounds can function as potential acetylcholinesterase inhibitor. Among 12 synthesized derivatives, compound 4a with ortho chlorine moiety as electron withdrawing group exhibited the highest potency in these series (IC50 = 0.91 ± 0.045 μM) compared to donepezil (IC50 = 0.14 ± 0.03 μM). The results of the enzyme inhibition test (Ellman test) showed that electron withdrawing groups like Cl, F and NO2 can render the best effect at position ortho and para of the phenyl ring. But compound 4g with methoxy group at position 3(meta) afforded a favorable potency (IC50 = 5.5 ± 0.7 μM). Furthermore, docking study confirmed a same binding mode like donepezil for compound 4a. Conclusions Synthesized compounds 4a-4l could be proposed as potential anticholinesterase agents. PMID:23758724

Rapid antidepressant actions of scopolamine: Role of medial prefrontal cortex and M1-subtype muscarinic acetylcholine receptors.

PubMed

Navarria, Andrea; Wohleb, Eric S; Voleti, Bhavya; Ota, Kristie T; Dutheil, Sophie; Lepack, Ashley E; Dwyer, Jason M; Fuchikami, Manabu; Becker, Astrid; Drago, Filippo; Duman, Ronald S

2015-10-01

Clinical studies demonstrate that scopolamine, a non-selective muscarinic acetylcholine receptor (mAchR) antagonist, produces rapid therapeutic effects in depressed patients, and preclinical studies report that the actions of scopolamine require glutamate receptor activation and the mechanistic target of rapamycin complex 1 (mTORC1). The present study extends these findings to determine the role of the medial prefrontal cortex (mPFC) and specific muscarinic acetylcholine receptor (M-AchR) subtypes in the actions of scopolamine. The administration of scopolamine increases the activity marker Fos in the mPFC, including the infralimbic (IL) and prelimbic (PrL) subregions. Microinfusions of scopolamine into either the IL or the PrL produced significant antidepressant responses in the forced swim test, and neuronal silencing of IL or PrL blocked the antidepressant effects of systemic scopolamine. The results also demonstrate that the systemic administration of a selective M1-AChR antagonist, VU0255035, produced an antidepressant response and stimulated mTORC1 signaling in the PFC, similar to the actions of scopolamine. Finally, we used a chronic unpredictable stress model as a more rigorous test of rapid antidepressant actions and found that a single dose of scopolamine or VU0255035 blocked the anhedonic response caused by CUS, an effect that requires the chronic administration of typical antidepressants. Taken together, these findings indicate that mPFC is a critical mediator of the behavioral actions of scopolamine and identify the M1-AChR as a therapeutic target for the development of novel and selective rapid-acting antidepressants. Copyright © 2015 Elsevier Inc. All rights reserved.

Topological dispositions of lysine. alpha. 380 and lysine. gamma. 486 in the acetylcholine receptor from Torpedo californica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dwyer, B.P.

1991-04-23

The locations have been determined, with respect to the plasma membrane, of lysine {alpha}380 and lysine {gamma}486 in the {alpha} subunit and the {gamma} subunit, respectively, of the nicotinic acetylcholine receptor from Torpedo californica. Immunoadsorbents were constructed that recognize the carboxy terminus of the peptide GVKYIAE released by proteolytic digestion from positions 378-384 in the amino acid sequence of the {alpha} subunit of the acetylcholine receptor and the carboxy terminus of the peptide KYVP released by proteolytic digestion from positions 486-489 in the amino acid sequence of the {gamma} subunit. They were used to isolate these peptides from proteolytic digestsmore » of polypeptides from the acetylcholine receptor. Sealed vesicles containing the native acetylcholine receptor were labeled with pyridoxal phosphate and sodium ({sup 3}H)-borohydride. The effect of saponin on the incorporation of pyridoxamine phosphate into lysine {alpha}380 and lysine {gamma}486 from the acetylcholine receptor in these vesicles was assessed with the immunoadsorbents. The conclusions that follow from these results are that lysine {alpha}380 is on the inside surface of a vesicle and lysine {gamma}486 is on the outside surface. Because a majority (85%) of the total binding sites for {alpha}-bungarotoxin bind the toxin in the absence of saponin, the majority of the vesicles are right side out with the inside of the vesicle corresponding to the cytoplasmic surface and the outside of the vesicle corresponding to the extracytoplasmic, synaptic surface. Because lysine {alpha}380 and lysine {gamma}486 lie on opposite sides of the membrane, a membrane-spanning segment must be located between the two positions occupied by these two amino acids in the common sequence of a polypeptide of the acetylcholine receptor.« less

PI3K/Akt-Independent NOS/HO Activation Accounts for the Facilitatory Effect of Nicotine on Acetylcholine Renal Vasodilations: Modulation by Ovarian Hormones

PubMed Central

Gohar, Eman Y.; El-gowilly, Sahar M.; El-Gowelli, Hanan M.; El-Demellawy, Maha A.; El-Mas, Mahmoud M.

2014-01-01

We investigated the effect of chronic nicotine on cholinergically-mediated renal vasodilations in female rats and its modulation by the nitric oxide synthase (NOS)/heme oxygenase (HO) pathways. Dose-vasodilatory response curves of acetylcholine (0.01–2.43 nmol) were established in isolated phenylephrine-preconstricted perfused kidneys obtained from rats treated with or without nicotine (0.5–4.0 mg/kg/day, 2 weeks). Acetylcholine vasodilations were potentiated by low nicotine doses (0.5 and 1 mg/kg/day) in contrast to no effect for higher doses (2 and 4 mg/kg/day). The facilitatory effect of nicotine was acetylcholine specific because it was not observed with other vasodilators such as 5′-N-ethylcarboxamidoadenosine (NECA, adenosine receptor agonist) or papaverine. Increases in NOS and HO-1 activities appear to mediate the nicotine-evoked enhancement of acetylcholine vasodilation because the latter was compromised after pharmacologic inhibition of NOS (L-NAME) or HO-1 (zinc protoporphyrin, ZnPP). The renal protein expression of phosphorylated Akt was not affected by nicotine. We also show that the presence of the two ovarian hormones is necessary for the nicotine augmentation of acetylcholine vasodilations to manifest because nicotine facilitation was lost in kidneys of ovariectomized (OVX) and restored after combined, but not individual, supplementation with medroxyprogesterone acetate (MPA) and estrogen (E2). Together, the data suggests that chronic nicotine potentiates acetylcholine renal vasodilation in female rats via, at least partly, Akt-independent HO-1 upregulation. The facilitatory effect of nicotine is dose dependent and requires the presence of the two ovarian hormones. PMID:24733557

Agonist activation of α7 nicotinic acetylcholine receptors via an allosteric transmembrane site

PubMed Central

Gill, JasKiran K.; Savolainen, Mari; Young, Gareth T.; Zwart, Ruud; Sher, Emanuele; Millar, Neil S.

2011-01-01

Conventional nicotinic acetylcholine receptor (nAChR) agonists, such as acetylcholine, act at an extracellular “orthosteric” binding site located at the interface between two adjacent subunits. Here, we present evidence of potent activation of α7 nAChRs via an allosteric transmembrane site. Previous studies have identified a series of nAChR-positive allosteric modulators (PAMs) that lack agonist activity but are able to potentiate responses to orthosteric agonists, such as acetylcholine. It has been shown, for example, that TQS acts as a conventional α7 nAChR PAM. In contrast, we have found that a compound with close chemical similarity to TQS (4BP-TQS) is a potent allosteric agonist of α7 nAChRs. Whereas the α7 nAChR antagonist metyllycaconitine acts competitively with conventional nicotinic agonists, metyllycaconitine is a noncompetitive antagonist of 4BP-TQS. Mutation of an amino acid (M253L), located in a transmembrane cavity that has been proposed as being the binding site for PAMs, completely blocks agonist activation by 4BP-TQS. In contrast, this mutation had no significant effect on agonist activation by acetylcholine. Conversely, mutation of an amino acid located within the known orthosteric binding site (W148F) has a profound effect on agonist potency of acetylcholine (resulting in a shift of ∼200-fold in the acetylcholine dose-response curve), but had little effect on the agonist dose-response curve for 4BP-TQS. Computer docking studies with an α7 homology model provides evidence that both TQS and 4BP-TQS bind within an intrasubunit transmembrane cavity. Taken together, these findings provide evidence that agonist activation of nAChRs can occur via an allosteric transmembrane site. PMID:21436053

Comparison of Extracellular Striatal Acetylcholine and Brain Seizure Activity Following Acute Exposure to the Nerve Agents Cyclosarin and Tabun in Freely Moving Guinea Pigs

DTIC Science & Technology

2010-01-01

Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Comparison of extracellular striatal acetylcholine and brain seizure activity following...lethality; nerve agents; organophosphorus compounds; seizure activity ; tabun 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER...acetylcholine and brain seizure activity following acute exposure to the nerve agents cyclosarin and tabun in freely moving guinea pigs John C

Coupling the Torpedo microplate-receptor binding assay with mass spectrometry to detect cyclic imine neurotoxins.

PubMed

Aráoz, Rómulo; Ramos, Suzanne; Pelissier, Franck; Guérineau, Vincent; Benoit, Evelyne; Vilariño, Natalia; Botana, Luis M; Zakarian, Armen; Molgó, Jordi

2012-12-04

Cyclic imine neurotoxins constitute an emergent family of neurotoxins of dinoflagellate origin that are potent antagonists of nicotinic acetylcholine receptors. We developed a target-directed functional method based on the mechanism of action of competitive agonists/antagonists of nicotinic acetylcholine receptors for the detection of marine cyclic imine neurotoxins. The key step for method development was the immobilization of Torpedo electrocyte membranes rich in nicotinic acetylcholine receptors on the surface of microplate wells and the use of biotinylated-α-bungarotoxin as tracer. Cyclic imine neurotoxins competitively inhibit biotinylated-α-bungarotoxin binding to Torpedo-nicotinic acetylcholine receptors in a concentration-dependent manner. The microplate-receptor binding assay allowed rapid detection of nanomolar concentrations of cyclic imine neurotoxins directly in shellfish samples. Although highly sensitive and specific for the detection of neurotoxins targeting nicotinic acetylcholine receptors as a class, the receptor binding assay cannot identify a given analyte. To address the low selectivity of the microplate-receptor binding assay, the cyclic imine neurotoxins tightly bound to the coated Torpedo nicotinic receptor were eluted with methanol, and the chemical nature of the eluted ligands was identified by mass spectrometry. The immobilization of Torpedo electrocyte membranes on the surface of microplate wells proved to be a high-throughput format for the survey of neurotoxins targeting nicotinic acetylcholine receptors directly in shellfish matrixes with high sensitivity and reproducibility.

Effects of the 5-HT6 receptor antagonist idalopirdine on extracellular levels of monoamines, glutamate and acetylcholine in the rat medial prefrontal cortex.

PubMed

Mørk, Arne; Russell, Rasmus Vinther; de Jong, Inge E M; Smagin, Gennady

2017-03-15

Idalopirdine (Lu AE58054) is a high affinity and selective antagonist for the human serotonin 5-HT 6 receptor (K i 0.83nM) in phase III development for mild-to-moderate Alzheimer's disease as an adjunct therapy to acetylcholinesterase inhibitors (AChEIs). We have studied the effects of idalopirdine on extracellular levels of monoamines, glutamate and acetylcholine in the medial prefrontal cortex (mPFC) of freely-moving rats using microdialysis. Idalopirdine (10mg/kg p.o.) increased extracellular levels of dopamine, noradrenaline and glutamate in the mPFC and showed a trend to increase serotonin levels. No effect was observed on acetylcholine levels. The AChEI donepezil (1.3mg/kg s.c.) significantly increased the levels of acetylcholine. Pretreatment with idalopirdine 2h prior to donepezil administration potentiated the effect of donepezil on extracellular acetylcholine levels. The idalopirdine potentiation of donepezil-induced increase in acetylcholine levels was also observed during local infusion of idalopirdine (6µg/ml) into the mPFC by reverse dialysis. The data from the current study may provide a mechanistic model for the pro-cognitive effects observed with administration of idalopirdine in donepezil-treated patients with Alzheimer's disease observed in the phase 2 studies (Wilkinson et al. 2014). Copyright © 2017 Elsevier B.V. All rights reserved.

Acetylcholine Attenuates Hydrogen Peroxide-Induced Intracellular Calcium Dyshomeostasis Through Both Muscarinic and Nicotinic Receptors in Cardiomyocytes.

PubMed

Palee, Siripong; Apaijai, Nattayaporn; Shinlapawittayatorn, Krekwit; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2016-01-01

Oxidative stress induced intracellular Ca2+ overload plays an important role in the pathophysiology of several heart diseases. Acetylcholine (ACh) has been shown to suppress reactive oxygen species generation during oxidative stress. However, there is little information regarding the effects of ACh on the intracellular Ca2+ regulation in the presence of oxidative stress. Therefore, we investigated the effects of ACh applied before or after hydrogen peroxide (H2O2) treatment on the intracellular Ca2+ regulation in isolated cardiomyocytes. Single ventricular myocytes were isolated from the male Wistar rats for the intracellular Ca2+ transient study by a fluorimetric ratio technique. H2O2 significantly decreased both of intracellular Ca2+ transient amplitude and decay rate. ACh applied before, but not after, H2O2 treatment attenuated the reduction of intracellular Ca2+ transient amplitude and decay rate. Both atropine (a muscarinic acetylcholine receptor blocker) and mecamylamine (a nicotinic acetylcholine receptor blocker) significantly decreased the protective effects of acetylcholine on the intracellular Ca2+ regulation. Moreover, the combination of atropine and mecamylamine completely abolished the protective effects of acetylcholine on intracellular Ca2+ transient amplitude and decay rate. ACh pretreatment attenuates H2O2-induced intracellular Ca2+ dyshomeostasis through both muscarinic and nicotinic receptors. © 2016 The Author(s) Published by S. Karger AG, Basel.

The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction.

PubMed

Obis, Teresa; Hurtado, Erica; Nadal, Laura; Tomàs, Marta; Priego, Mercedes; Simon, Anna; Garcia, Neus; Santafe, Manel M; Lanuza, Maria A; Tomàs, Josep

2015-12-01

Various protein kinase C (PKC) isoforms contribute to the phosphorylating activity that modulates neurotransmitter release. In previous studies we showed that nPKCε is confined in the presynaptic site of the neuromuscular junction and its presynaptic function is activity-dependent. Furthermore, nPKCε regulates phorbol ester-induced acetylcholine release potentiation, which further indicates that nPKCε is involved in neurotransmission. The present study is designed to examine the nPKCε involvement in transmitter release at the neuromuscular junction. We use the specific nPKCε translocation inhibitor peptide εV1-2 and electrophysiological experiments to investigate the involvement of this isoform in acetylcholine release. We observed that nPKCε membrane translocation is key to the synaptic potentiation of NMJ, being involved in several conditions that upregulate PKC isoforms coupling to acetylcholine (ACh) release (incubation with high Ca(2+), stimulation with phorbol esters and protein kinase A, stimulation with adenosine 3',5'-cyclic monophosphorothioate, 8-Bromo-, Rp-isomer, sodium salt -Sp-8-BrcAMP-). In all these conditions, preincubation with the nPKCε translocation inhibitor peptide (εV1-2) impairs PKC coupling to acetylcholine release potentiation. In addition, the inhibition of nPKCε translocation and therefore its activity impedes that presynaptic muscarinic autoreceptors and adenosine autoreceptors modulate transmitter secretion. Together, these results point to the importance of nPKCε isoform in the control of acetylcholine release in the neuromuscular junction.

Coupling the Torpedo Microplate-Receptor Binding Assay with Mass Spectrometry to Detect Cyclic Imine Neurotoxins

PubMed Central

Aráoz, Rómulo; Ramos, Suzanne; Pelissier, Franck; Guérineau, Vincent; Benoit, Evelyne; Vilariño, Natalia; Botana, Luis M.; Zakarian, Armen; Molgó, Jordi

2014-01-01

Cyclic imine neurotoxins constitute an emergent family of neurotoxins of dinoflagellate origin that are potent antagonists of nicotinic acetylcholine receptors. We developed a target-directed functional method based on the mechanism of action of competitive agonists/antagonists of nicotinic acetylcholine receptors for the detection of marine cyclic imine neurotoxins. The key step for method development was the immobilization of Torpedo electrocyte membranes rich in nicotinic acetylcholine receptors on the surface of microplate wells and the use of biotinylated-α-bungarotoxin as tracer. Cyclic imine neurotoxins competitively inhibit biotinylated-α-bungarotoxin binding to Torpedo-nicotinic acetylcholine receptors in a concentration-dependent manner. The microplate-receptor binding assay allowed rapid detection of nanomolar concentrations of cyclic imine neurotoxins directly in shellfish samples. Although highly sensitive and specific for the detection of neurotoxins targeting nicotinic acetylcholine receptors as a class, the receptor binding assay cannot identify a given analyte. To address the low selectivity of the microplate-receptor binding assay, the cyclic imine neurotoxins tightly bound to the coated Torpedo nicotinic receptor were eluted with methanol, and the chemical nature of the eluted ligands was identified by mass spectrometry. The immobilization of Torpedo electrocyte membranes on the surface of microplate wells proved to be a high-throughput format for the survey of neurotoxins targeting nicotinic acetylcholine receptors directly in shellfish matrixes with high sensitivity and reproducibility. PMID:23131021

Key role of striatal cholinergic interneurons in processes leading to arrest of motor stereotypies.

PubMed

Aliane, Verena; Pérez, Sylvie; Bohren, Yohann; Deniau, Jean-Michel; Kemel, Marie-Louise

2011-01-01

Motor stereotypy is a key symptom of various disorders such as Tourette's syndrome and punding. Administration of nicotine or cholinesterase inhibitors is effective in treating some of these symptoms. However, the role of cholinergic transmission in motor stereotypy remains unknown. During strong cocaine-induced motor stereotypy, we showed earlier that increased dopamine release results in decreased acetylcholine release in the territory of the dorsal striatum related to the prefrontal cortex. Here, we investigated the role of striatal cholinergic transmission in the arrest of motor stereotypy. Analysis of N-methyl-d-aspartic acid-evoked release of dopamine and acetylcholine during declining intensity of motor stereotypy revealed a dissociation between dopamine and acetylcholine release. Whereas dopamine release remained increased, the inhibition of acetylcholine release decreased, mirroring the time course of motor stereotypy. Furthermore, pharmacological treatments restoring striatal acetylcholine release (raclopride, dopamine D2 antagonist; intraperitoneal or local injection in prefrontal territory of the dorsal striatum) rapidly stopped motor stereotypy. In contrast, pharmacological treatments that blocked the post-synaptic effects of acetylcholine (scopolamine, muscarinic antagonist; intraperitoneal or striatal local injection) or induced degeneration of cholinergic interneurons (AF64A, cholinergic toxin) in the prefrontal territory of the dorsal striatum robustly prolonged the duration of strong motor stereotypy. Thus, we propose that restoration of cholinergic transmission in the prefrontal territory of the dorsal striatum plays a key role in the arrest of motor stereotypy.

Potential roles of cholinergic modulation in the neural coding of location and movement speed

PubMed Central

Dannenberg, Holger; Hinman, James R.; Hasselmo, Michael E.

2016-01-01

Behavioral data suggest that cholinergic modulation may play a role in certain aspects of spatial memory, and neurophysiological data demonstrate neurons that fire in response to spatial dimensions, including grid cells and place cells that respond on the basis of location and running speed. These neurons show firing responses that depend upon the visual configuration of the environment, due to coding in visually-responsive regions of the neocortex. This review focuses on the physiological effects of acetylcholine that may influence the sensory coding of spatial dimensions relevant to behavior. In particular, the local circuit effects of acetylcholine within the cortex regulate the influence of sensory input relative to internal memory representations, via presynaptic inhibition of excitatory and inhibitory synaptic transmission, and the modulation of intrinsic currents in cortical excitatory and inhibitory neurons. In addition, circuit effects of acetylcholine regulate the dynamics of cortical circuits including oscillations at theta and gamma frequencies. These effects of acetylcholine on local circuits and network dynamics could underlie the role of acetylcholine in coding of spatial information for the performance of spatial memory tasks. PMID:27677935

Are acetylcholine-induced acetyl groups driving fuel cells in the systems of transducin, t and G proteins?

PubMed

Nyberg-Swenson, B E

2002-05-01

Life is completely dependent on a support of energy which is generated by the direct absorption of light or by the reduction of oxygen. Metabolized food yields ac(et)yl groups which are utilized in the reduction of oxygen with the assistance of many other compounds. Acetylcholine appears to be an important substance for the transportation of acetyl groups. Acetylcholine activates systems regulated by transducin, t and G proteins, probably Se enzymes, reacting by similar mechanisms in triggered reactions ending in nerve or muscle signals. These activations are performed by GTP (or ATP), probably resulting from the reactions of acetylcholine-induced acetyl groups. The inactivation-activation states of these systems are regulated by changes of GTP to cGMP to GMP which form a loop.Diminished support of energy to systems, because of impaired charge transfer to oxygen, may be responsible for many diseases. For example, there is a low level of acetylcholine in the brains of patients with Alzheimer's disease. Copyright 2002 Elsevier Science Ltd. All Rights reserved.

Sorting receptor Rer1 controls surface expression of muscle acetylcholine receptors by ER retention of unassembled alpha-subunits.

PubMed

Valkova, Christina; Albrizio, Marina; Röder, Ira V; Schwake, Michael; Betto, Romeo; Rudolf, Rüdiger; Kaether, Christoph

2011-01-11

The nicotinic acetylcholine receptor of skeletal muscle is composed of five subunits that are assembled in a stepwise manner. Quality control mechanisms ensure that only fully assembled receptors reach the cell surface. Here, we show that Rer1, a putative Golgi-ER retrieval receptor, is involved in the biogenesis of acetylcholine receptors. Rer1 is expressed in the early secretory pathway in the myoblast line C2C12 and in mouse skeletal muscle, and up-regulated during myogenesis. Upon down-regulation of Rer1 in C2C12 cells, unassembled acetylcholine receptor α-subunits escape from the ER and are transported to the plasma membrane and lysosomes, where they are degraded. As a result, the amount of fully assembled receptor at the cell surface is reduced. In vivo Rer1 knockdown and genetic inactivation of one Rer1 allele lead to significantly smaller neuromuscular junctions in mice. Our data show that Rer1 is a functionally important unique factor that controls surface expression of muscle acetylcholine receptors by localizing unassembled α-subunits to the early secretory pathway.

Interactions between acetylcholine, 5-hydroxytryptamine, nicotine and morphine on isolated rabbit atria

PubMed Central

Chittal, S. M.; Dadkar, N. K.; Gaitondé, B. B.

1968-01-01

1. The effects of 5-hydroxytryptamine (5-HT) and morphine on the responses to acetylcholine and nicotine of isolated rabbit atria were studied. 2. 5-Hydroxytryptamine (10 μg/ml.) and morphine (20 μg/ml.) blocked the negative chronotropic and inotropic actions of acetylcholine. 3. Nicotine (20 μg/ml.) produced stimulation of the atria, which was blocked by dichlorisoprenaline, morphine, 5-HT, bretylium and hemicholinium. Hemicholinium block was reversed by choline. 4. In reserpinized preparations, nicotine produced inhibition of atria and this action was also blocked by atropine, 5-HT and morphine. Inhibition induced by nicotine was potentiated by physostigmine. 5. 5-Hydroxytryptamine (20 μg/ml.) produced stimulation of atria. This was blocked by bretylium and reduced by hemicholinium. Hemicholinium block was reversed by choline. 6. It is concluded that 5-HT in low concentrations acts as a weak agonist at the cholinoceptive receptors and therefore blocks the action of acetylcholine. Furthermore, nicotine and larger doses of 5-HT have actions on ganglionic structures and liberate acetylcholine, which in turn releases catecholamines. PMID:4386371

Local cardiac effects of substance P: roles of acetylcholine and noradrenaline.

PubMed Central

Chiao, H; Caldwell, R W

1995-01-01

1. The local cardiac actions of substance P were examined in isolated perfused hearts and atria of the guinea-pig. 2. In both hearts and right atria, substance P caused negative inotropic and chronotropic effects. 3. Atropine (10(-6) M) or depletion of acetylcholine, by electrical stimulation and hemicholinium-3 perfusion, significantly attenuated the negative inotropic and chronotropic effects of substance P. alpha- and beta-adrenoceptor blockade by nadolol and phentolamine (10(-6) M each) did not prevent the negative inotropic and chronotropic effects of substance P. This indicates that cholinergic neurones, but not adrenergic neurones, partially mediate the effects of substance P. 4. There was no significant difference in the effects of substance P observed between groups with acetylcholine depletion and with cholinoceptor blockade. This suggests that substance P elicits its effects mainly through release of acetylcholine. 5. These results indicate that substance P has negative inotropic and chronotropic effects in guinea-pig hearts and right atria mediated partly by release of acetylcholine. Substance P also appears to have direct effects on cardiac tissue. PMID:7533612

An extract of lionfish (Pterois volitans) spine tissue contains acetylcholine and a toxin that affects neuromuscular transmission.

PubMed

Cohen, A S; Olek, A J

1989-01-01

A soluble toxic extract derived from spine tissue of the lionfish (Pterois volitans) decreased heart rate and force of contraction in isolated clam and frog hearts. These actions were due to the presence of micromolar concentrations of acetylcholine in the extract. Toxicity was retained after hydrolysis of acetylcholine by exogenous acetylcholinesterase, but heart function was no longer affected. Toxin treated in this way induced muscle fibrillation in an isolated nerve-muscle preparation, followed by blockade of neuromuscular transmission. Bursts of transient depolarizations were recorded at the muscle endplate shortly after toxin addition that correlated in time with the duration of toxin-induced muscle fibrillation. These effects are thought to be due to the increased release and then depletion of acetylcholine from the nerve terminal.

Acetylcholine beyond bronchoconstriction: roles in inflammation and remodeling.

PubMed

Kistemaker, Loes E M; Gosens, Reinoud

2015-03-01

Acetylcholine is the primary parasympathetic neurotransmitter in the airways, where it not only induces bronchoconstriction and mucus secretion, but also regulates airway inflammation and remodeling. In this review, we propose that these effects are all primarily mediated via the muscarinic M3 receptor. Acetylcholine promotes inflammation and remodeling via direct effects on airway cells, and via mechanical stress applied to the airways sequential to bronchoconstriction. The effects on inflammation and remodeling are regulated by both neuronal and non-neuronal acetylcholine. Taken together, we believe that the combined effects of anticholinergic therapy on M3-mediated bronchoconstriction, mucus secretion, inflammation, and remodeling may account for the positive outcome of treatment with these drugs for patients with chronic pulmonary obstructive disease (COPD) or asthma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neurobiology of nAChRs and cognition: A mini review of Dr. Jerry J. Buccafusco's contributions over a 25 year career

PubMed Central

Terry, Alvin V.; Decker, Michael W.

2011-01-01

This review highlights some of the many contributions of the late Dr. Jerry J. Buccafusco to the neurobiology of nicotinic acetylcholine receptors (nAChRs) and cognition over a 25 year period. The article is written by two of Dr. Buccafusco's professional colleagues, one from academia and one from the pharmaceutical industry. While Dr. Buccafusco's expertise in the cholinergic field was extensive, his insights into the practical relevance of his work (with a long-term goal of formulating new drug development strategies) were unique, and a great asset to both the basic science community and pharmaceutical companies. In 1988, Dr. Buccafusco's laboratory was the first to report the cognitive enhancing action of low doses of nicotine in non-human primates. Since that time he studied a large number of novel pro-cognitive agents from several pharmacological classes in rodents as well as monkeys. Based on years of observing paradoxical effects of nicotinic ligands in vitro and in vivo, Dr. Buccafusco made the provocative argument that it might be possible to develop new chemical entities (with pro-cognitive actions) that have the ability to desensitize nAChRs without producing an antecedent agonist action. Some of his more recent work focused on development of single molecular entities that act on multiple CNS targets (including nAChRs) to enhance cognition, provide neuroprotection, and/or provide additional therapeutic actions (e.g., antipsychotic effects). Dr. Buccafusco's influence will live on in the work of the numerous graduate students, postdoctoral fellows, and junior faculty that he mentored over the years who now serve in prestigious positions throughout the world. PMID:21684265

Convergent evidence for abnormal striatal synaptic plasticity in dystonia

PubMed Central

Peterson, David A.; Sejnowski, Terrence J.; Poizner, Howard

2010-01-01

Dystonia is a functionally disabling movement disorder characterized by abnormal movements and postures. Although substantial recent progress has been made in identifying genetic factors, the pathophysiology of the disease remains a mystery. A provocative suggestion gaining broader acceptance is that some aspect of neural plasticity may be abnormal. There is also evidence that, at least in some forms of dystonia, sensorimotor “use” may be a contributing factor. Most empirical evidence of abnormal plasticity in dystonia comes from measures of sensorimotor cortical organization and physiology. However, the basal ganglia also play a critical role in sensorimotor function. Furthermore, the basal ganglia are prominently implicated in traditional models of dystonia, are the primary targets of stereotactic neurosurgical interventions, and provide a neural substrate for sensorimotor learning influenced by neuromodulators. Our working hypothesis is that abnormal plasticity in the basal ganglia is a critical link between the etiology and pathophysiology of dystonia. In this review we set up the background for this hypothesis by integrating a large body of disparate indirect evidence that dystonia may involve abnormalities in synaptic plasticity in the striatum. After reviewing evidence implicating the striatum in dystonia, we focus on the influence of two neuromodulatory systems: dopamine and acetylcholine. For both of these neuromodulators, we first describe the evidence for abnormalities in dystonia and then the means by which it may influence striatal synaptic plasticity. Collectively, the evidence suggests that many different forms of dystonia may involve abnormal plasticity in the striatum. An improved understanding of these altered plastic processes would help inform our understanding of the pathophysiology of dystonia, and, given the role of the striatum in sensorimotor learning, provide a principled basis for designing therapies aimed at the dynamic processes linking etiology to pathophysiology of the disease. PMID:20005952

Effects of aerosolised substance P on lung resistance in guinea-pigs: a comparison between inhibition of neutral endopeptidase and angiotensin-converting enzyme.

PubMed

Lötvall, J O; Skoogh, B E; Barnes, P J; Chung, K F

1990-05-01

1. We have examined in guinea-pigs, in vivo, the effects of inhibition of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) on the airway response to aerosolised substance P (SP). We aerosolised captopril (4.6 mM, 60 breaths; 210 nmol) to inhibit ACE and acetorphan (0.3, 1 and 3 mM, 60 breaths; 9 nmol, 33 nmol and 110 nmol respectively) to inhibit NEP. We also examined the effect of the highest dose of acetorphan (110 nmol) on the response to aerosolised acetylcholine (ACh). 2. Responsiveness to SP (or ACh) was measured as the change in lung resistance (RL) induced by nebulisation of increasing concentrations of SP (or ACh) before and after treatment with the inhibitor. PC200, defined as the provocative concentration inducing an increase in RL of 200% above baseline was calculated for each challenge. 3. Administration of acetorphan before the second SP-challenge induced a dose-dependent decrease in PC200 for SP amounting to 1.8 (+/- 0.3) log units after treatment with 11 nmol acetorphan. Treatment with vehicle before the second SP-challenge or with 3 mM acetorphan before the second ACh-challenge had no significant effect on PC200. 4. Treatment with captopril (21 nmol) induced only a small, nonsignificant leftward shift of PC200 to SP (0.3 +/- 0.2 log units). 5. We conclude that a NEP-like enzyme, but not ACE, regulates the response to aerosolised SP. We suggest that the same is true for SP released endogenously from sensory nerve endings in the airway epithelial layer.

Effects of aerosolised substance P on lung resistance in guinea-pigs: a comparison between inhibition of neutral endopeptidase and angiotensin-converting enzyme.

PubMed Central

Lötvall, J. O.; Skoogh, B. E.; Barnes, P. J.; Chung, K. F.

1990-01-01

1. We have examined in guinea-pigs, in vivo, the effects of inhibition of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) on the airway response to aerosolised substance P (SP). We aerosolised captopril (4.6 mM, 60 breaths; 210 nmol) to inhibit ACE and acetorphan (0.3, 1 and 3 mM, 60 breaths; 9 nmol, 33 nmol and 110 nmol respectively) to inhibit NEP. We also examined the effect of the highest dose of acetorphan (110 nmol) on the response to aerosolised acetylcholine (ACh). 2. Responsiveness to SP (or ACh) was measured as the change in lung resistance (RL) induced by nebulisation of increasing concentrations of SP (or ACh) before and after treatment with the inhibitor. PC200, defined as the provocative concentration inducing an increase in RL of 200% above baseline was calculated for each challenge. 3. Administration of acetorphan before the second SP-challenge induced a dose-dependent decrease in PC200 for SP amounting to 1.8 (+/- 0.3) log units after treatment with 11 nmol acetorphan. Treatment with vehicle before the second SP-challenge or with 3 mM acetorphan before the second ACh-challenge had no significant effect on PC200. 4. Treatment with captopril (21 nmol) induced only a small, nonsignificant leftward shift of PC200 to SP (0.3 +/- 0.2 log units). 5. We conclude that a NEP-like enzyme, but not ACE, regulates the response to aerosolised SP. We suggest that the same is true for SP released endogenously from sensory nerve endings in the airway epithelial layer. PMID:1695534

Occupational hand-arm vibration syndrome in Korea.

PubMed

Yoo, Cheolin; Lee, Ji-Ho; Lee, Choong-Ryeol; Kim, Yangho; Lee, Hun; Choi, Younghee; Kim, Young Wook; Chae, Chang Ho; Kim, Hyokyoung; Koh, Sang Baek; Kim, Euna; Lee, Lu Jin; Lee, Kiyoung

2005-06-01

It is suspected that there is a large number of patients suffering from hand-arm vibration syndrome (HAVS) in Korea. However, no cases have been reported since 1992. This study was conducted to identify HAVS cases and determine the characteristics of the syndrome. In April 2001, the Busan, Ulsan, and Gyeong-Nam Province Occupational Disease Surveillance System (BUGODSS) was established to identify work-related HAVS and other occupational diseases. In the 2 years of this project, occupational physicians from five hospitals in these provinces collected information by way of interviews and questionnaires during mandatory occupational medical examinations. Among the initial 189 suspected HAVS cases, 58 volunteers were given cold-water provocation tests in order to diagnose the vascular component of the disorder. One hundred fifty-four approximately occupational HAVS cases were identified from ca. 21,000 workers. One hundred fifty about of these cases were male. The cases were most often found in workers from the shipbuilding industry, and the grinder was the most common source of vibration exposure. Cases of sensorineural disorder (SD) were more common than cases of vascular disorder (VD). The mean values of the finger skin temperature and its recovery rate at 5 min and 10 min after cold-water provocation were significantly lower in the group with the VD than in the group with the SD. We identified 154 occupational HAVS cases, although no cases have been reported during the occupational medical examinations mandated by the state. The majority of the cases were in workers that used grinders in the shipbuilding industry. We determined that peripheral VD and peripheral SD can progress independently of each other. We conclude that exposure to hand-transmitted vibration (HTV) and HAVS cases are common in shipbuilding industry in Korea. The recovery rate of finger skin temperature after cold-water provocation is one of the useful methods for diagnosing the vascular component of HAVS.

Guidelines for pre-clinical assessment of the acetylcholine receptor-specific passive transfer myasthenia gravis model - recommendations for methods and experimental designs

PubMed Central

Kusner, Linda L.; Losen, Mario; Vincent, Angela; Lindstrom, Jon; Tzartos, Socrates; Lazaridis, Konstantinos; Martinez-Martinez, Pilar

2015-01-01

Antibodies against the muscle acetylcholine receptor (AChR) are the most common cause of myasthenia gravis (MG). Passive transfer of AChR antibodies from MG patients into animals reproduces key features of human disease, including antigenic modulation of the AChR, complement-mediated damage of the neuromuscular junction, and muscle weakness. Similarly, AChR antibodies generated by active immunization in experimental autoimmune MG models can subsequently be passively transferred to other animals and induce weakness. The passive transfer model is useful to test therapeutic strategies aimed at the effector mechanism of the autoantibodies. Here we summarize published and unpublished experience using the AChR passive transfer MG model in mice, rats and rhesus monkeys, and give recommendations for the design of preclinical studies in order to facilitate translation of positive and negative results to improve MG therapies. PMID:25743217

Caffeine potentiates the enhancement by choline of striatal acetylcholine release

NASA Technical Reports Server (NTRS)

Johnson, D. A.; Ulus, I. H.; Wurtman, R. J.

1992-01-01

We investigated the effect of peripherally administered caffeine (50 mg/kg), choline (30, 60, or 120 mg/kg) or combinations of both drugs on the spontaneous release of acetylcholine (ACh) from the corpus striatum of anesthetized rats using in vivo microdialysis. Caffeine alone or choline in the 30 or 60 mg/kg dose failed to increase ACh in microdialysis samples; the 120 mg/kg choline dose significantly enhanced ACh during the 80 min following drug administration. Coadministration of caffeine with choline significantly increased ACh release after each of the choline doses tested. Peak microdialysate levels with the 120 mg/kg dose were increased 112% when caffeine was additionally administered, as compared with 54% without caffeine. These results indicate that choline administration can enhance spontaneous ACh release from neurons, and that caffeine, a drug known to block adenosine receptors on these neurons, can amplify the choline effect.

The action of the insecticide imidacloprid on the respiratory rhythm of an insect: the beetle Tenebrio molitor.

PubMed

Zafeiridou, Georgia; Theophilidis, George

2004-07-29

Imidacloprid is an insecticide which has the nicotinic acetylcholine receptors (nAChRs) as its primary site of action; acetylcholine is the major excitatory neurotransmitter in the insect central nervous system (CNS). In this study, the action of imidacloprid was tested using the synapses of the respiratory central pattern generator of the beetle Tenebrio molitor. The no observed effect concentration (NOEC) for imidacloprid was estimated to be between 0.001 and 0.010 microM. A concentration of 0.10 microM caused hyperexcitation in firing of the respiratory motoneurons, while the concentration of 1.00 microM caused an abrupt increase in their frequency and then a complete inhibition of the activity of the respiratory motoneurons. The possible implication of the action of such low concentrations of imidacloprid in the contraction of the respiratory muscles is also demonstrated and discussed.

Growth retardation and reduced growth hormone secretion in cystic fibrosis. Clinical observations from three CF centers.

PubMed

Ciro, D'Orazio; Padoan, Rita; Blau, Hannah; Marostica, Anna; Fuoti, Maurizio; Volpi, Sonia; Pilotta, Alba; Meyerovitch, Joseph; Sher, Daniel; Assael, Baroukh M

2013-03-01

Growth delay in cystic fibrosis is frequent and is usually the result of several interacting causes. It most often derives from severe respiratory impairment and severe malabsorption. There are however patients whose clinical condition is not severe enough to be held accountable for this phenomenon. We aimed at describing patients who showed growth delay, who were not affected by severe pulmonary disease or malabsorption and who, when tested, showed a reduced GH secretion after stimulation with conventional agents. We noticed a disproportionately large prevalence of growth hormone (GH) release deficit (GHRD) in pediatric cystic fibrosis (CF) patients. We examined all patients under our care in the period 2006-11, who were older than 5 and younger than 16 years old. We focussed on those who fell below the 3rd height percentile, or whose growth during the previous 18 months faltered by >2SD, and who did not present clinical conditions that could reasonably explain their failure to thrive. These patients were subjected to standard GH provocative tests. Out of 285 who matched the age criterion, 33 patients also matched the height percentile criterion. While 15/33 suffered clinical conditions that could reasonably explain their failure to thrive, 18/33 underwent GH release provocative tests and 12/18 showed a release deficit. We conclude that impaired GH secretion is more frequent among CF patients compared to the prevalence of GH deficiency in the general population and that GH release impairment may be an independent cause of growth delay in CF. Our findings are in agreement with recent studies that have described low GH levels in CF piglets and in neonates with CF [1]. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Children's self reported discomforts as participants in clinical research.

PubMed

Staphorst, Mira S; Hunfeld, Joke A M; van de Vathorst, Suzanne; Passchier, Jan; van Goudoever, Johannes B

2015-10-01

There is little empirical evidence on children's subjective experiences of discomfort during clinical research procedures. Therefore, Institutional Review Boards have limited empirical information to guide their decision-making on discomforts for children in clinical research. To get more insight into what children's discomforts are during clinical research procedures, we interviewed a group of children on this topic and also asked for suggestions to reduce possible discomforts. Forty-six children (aged 6-18) participating in clinical research studies (including needle-related procedures, food provocation tests, MRI scans, pulmonary function tests, questionnaires) were interviewed about their experiences during the research procedures. Thematic analysis was used to analyze the interviews. The discomforts of the interviewed children could be divided into two main groups: physical and mental discomforts. The majority experienced physical discomforts during the research procedures: pain, shortness of breath, nausea, itchiness, and feeling hungry, which were often caused by needle procedures, some pulmonary procedures, and food provocation tests. Mental discomforts included anxiousness because of anticipated pain and not knowing what to expect from a research procedure, boredom and tiredness during lengthy research procedures and waiting, and embarrassment during Tanner staging. Children's suggestions to reduce the discomforts of the research procedures were providing distraction (e.g. watching a movie or listening to music), providing age-appropriate information and shortening the duration of lengthy procedures. Our study shows that children can experience various discomforts during research procedures, and it provides information about how these discomforts can be reduced according to them. Further research is needed with larger samples to study the number of children that experience these mentioned discomforts during research procedures in a quantitative way. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ocular Myasthenia Gravis

MedlinePlus

... more likely to have seronegative MG (no measurable acetylcholine receptor antibodies) compared with people with generalized MG. ... trunk and limbs. For example, they have fewer acetylcholine receptors, which is where the defect occurs in ...

Cholinergic Modulation of the Hippocampus during Encoding and Retrieval of Tone/Shock-Induced Fear Conditioning

ERIC Educational Resources Information Center

Rogers, Jason L.; Kesner, Raymond P.

2004-01-01

We investigated the role of acetylcholine (ACh) during encoding and retrieval of tone/shock-induced fear conditioning with the aim of testing Hasselmo's cholinergic modulation model of encoding and retrieval using a task sensitive to hippocampal disruption. Lesions of the hippocampus impair acquisition and retention of contextual conditioning with…

Dynamic Changes in Acetylcholine Output in the Medial Striatum during Place Reversal Learning

ERIC Educational Resources Information Center

Ragozzino, Michael E.; Choi, Daniel

2004-01-01

The present studies explored the role of the medial striatum in learning when task contingencies change. Experiment 1 examined whether the medial striatum is involved in place reversal learning. Testing occurred in a modified cross-maze across two consecutive sessions. Injections of the local anesthetic, bupivacaine, into the medial striatum, did…

Facilitation of Memory for Extinction of Drug-Induced Conditioned Reward: Role of Amygdala and Acetylcholine

ERIC Educational Resources Information Center

Schroeder, Jason P.; Packard, Mark G.

2004-01-01

eThese experiments examined the effects of posttrial peripheral and intra-amygdala injections of the cholinergic muscarinic receptor agonist oxotremorine on memory consolidation underlying extinction of amphetamine conditioned place preference (CPP) behavior. Male Long-Evans rats were initially trained and tested for an amphetamine (2 mg/kg) CPP.…

Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring

PubMed Central

2011-01-01

The ability of targeted and nontargeted metabolomics to discover chronic ecotoxicological effects is largely unexplored. Fenitrothion, an organophosphate pesticide, is categorized as a “red list” pollutant, being particularly hazardous to aquatic life. It acts primarily as a cholinesterase inhibitor, but evidence suggests it can also act as an androgen receptor antagonist. Whole-organism fenitrothion-induced toxicity is well-established, but information regarding target and off-target molecular toxicities is limited. Here we study the molecular responses of male roach (Rutilus rutilus) exposed to fenitrothion, including environmentally realistic concentrations, for 28 days. Acetylcholine was assessed in brain; steroid metabolism was measured in testes and plasma; and NMR and mass spectrometry-based metabolomics were conducted on testes and liver to discover off-target toxicity. O-demethylation was confirmed as a major route of pesticide degradation. Fenitrothion significantly depleted acetylcholine, confirming its primary mode of action, and 11-ketotestosterone in plasma and cortisone in testes, showing disruption of steroid metabolism. Metabolomics revealed significant perturbations to the hepatic phosphagen system and previously undocumented effects on phenylalanine metabolism in liver and testes. On the basis of several unexpected molecular responses that were opposite to the anticipated acute toxicity, we propose that chronic pesticide exposure induces an adapting phenotype in roach, which may have considerable implications for interpreting molecular biomarker responses in field-sampled fish. PMID:21410251

Use of Monoclonal Antibodies to Study the Structure and Function of Nicotinic Acetylcholine Receptors on Electric Organ and Muscle and to Determine the Structure of Nicotinic Acetylcholine Receptors on Neurons

DTIC Science & Technology

1988-03-16

receptors in muscle is responsible for the muscular weakness characteristic of myasthenia gravis . Some insecticides can act like chemical warfare...expresses muscle-like acetyi-.holine receptor by observing that autoantibodies from myasthenia gravis patients reacted as well with these receptors as...Antibodies in sera from patients with myasthenia gravis do not bind to acetylcholine receptors from human brain. J Neuroimmunol 16:205-213. 21. Whiting

Pharmacological Basis for Use of Armillaria mellea Polysaccharides in Alzheimer's Disease: Antiapoptosis and Antioxidation

PubMed Central

An, Shengshu; Lu, Wenqian; Zhang, Yongfeng; Yuan, Qingxia

2017-01-01

Armillaria mellea, an edible fungus, exhibits various pharmacological activities, including antioxidant and antiapoptotic properties. However, the effects of A. mellea on Alzheimer's disease (AD) have not been systemically reported. The present study aimed to explore the protective effects of mycelium polysaccharides (AMPS) obtained from A. mellea, especially AMPSc via 70% ethanol precipitation in a L-glutamic acid- (L-Glu-) induced HT22 cell apoptosis model and an AlCl3 plus D-galactose- (D-gal-) induced AD mouse model. AMPSc significantly enhanced cell viability, suppressed nuclear apoptosis, inhibited intracellular reactive oxygen species accumulation, prevented caspase-3 activation, and restored mitochondrial membrane potential (MMP). In AD mice, AMPSc enhanced horizontal movements in an autonomic activity test, improved endurance times in a rotarod test, and decreased escape latency time in a water maze test. Furthermore, AMPSc reduced the apoptosis rate, amyloid beta (Aβ) deposition, oxidative damage, and p-Tau aggregations in the AD mouse hippocampus. The central cholinergic system functions in AD mice improved after a 4-week course of AMPSc administration, as indicated by enhanced acetylcholine (Ach) and choline acetyltransferase (ChAT) concentrations, and reduced acetylcholine esterase (AchE) levels in serum and hypothalamus. Our findings provide experimental evidence suggesting A. mellea as a neuroprotective candidate for treating or preventing neurodegenerative diseases. PMID:29081887

Anaesthetic modulation of nicotinic ion channel kinetics in bovine chromaffin cells.

PubMed Central

Charlesworth, P; Richards, C D

1995-01-01

1. We have investigated the action of the anaesthetics methoxyflurane, methohexitone and etomidate on the nicotinic acetylcholine receptor channel of bovine adrenal chromaffin cells using the whole cell patch clamp technique. 2. Spectral analysis of macroscopic currents evoked by 25 microM carbachol revealed that each of the agents tested reduced the lifetime of the channel open state in a dose-dependent manner. The whole cell current was inhibited in a concentration-dependent fashion by each agent. 3. Channel gating parameters were calculated from single channel studies and the results used to test models explaining the modulation of nicotinic acetylcholine receptor channels by anaesthetics. 4. Each of the agents studied reduced the mean channel open time in a concentration-dependent manner. Anaesthetic concentrations reducing mean open time by 50% were: 370 microM methoxyflurane, 30 microM methohexitone or 23 microM etomidate. 5. Methohexitone and etomidate produced an increase in the number of brief closures within bursts, while no such increase was observed with methoxyflurane. Despite these inter-burst gaps, mean burst length was reduced by each of the agents tested. 6. It is concluded that a simple sequential blocking model fails to account for the action of these anaesthetics. An extended model, in which blocked channels can close, may be applicable. PMID:7773553

Understanding Alzheimer's

MedlinePlus

... donepezil), and Cognex (tacrine). They are known as cholinesterase inhibitors. Scientists believe they prevent the breakdown of acetylcholine, ... the brain produces less and less acetylcholine; therefore, cholinesterase inhibitors may eventually lose their effect. Treatment for Moderate ...

Experimentally Assessed Reactive Aggression in Borderline Personality Disorder

PubMed Central

Kogan-Goloborodko, Olga; Brügmann, Elisabeth; Repple, Jonathan; Habel, Ute; Clemens, Benjamin

2016-01-01

Approximately 73% of patients suffering from Borderline personality disorder (BPD) exhibit aggressive behaviour, which severely hinders therapeutic work and clinical improvement. Because the underlying mechanisms of aggression in BPD are not yet completely understood, additional research in this domain has a high clinical and scientific relevance. We employed a modified version of the Taylor Aggression Paradigm (mTAP), in order to examine for the first time whether this task can be used to differentiate between BPD patients and healthy controls with regard to reactive aggression. In the mTAP, the amount of money subtracted by a virtual opponent was categorized into ‘low’ (10–20 cents) and ‘high’ (80–100 cents) provocations, enabling us to compare how much money BPD patients and healthy controls subtracted (i.e., how aggressively participants responded) following high and low provocation trials. Our results showed that, compared to healthy controls, BPD patients showed higher overall aggression, higher aggression after high provocation trials, as well as a larger difference between high and low provocation trials. This finding was corroborated by a neuropsychological assessment, demonstrating higher levels of aggression and impulsivity in BPD patients. Interestingly, reactive aggression in the mTAP was positively correlated with symptom severity and impulsivity in BPD patients. We suggest that the mTAP provides a valuable tool allowing psychiatrists to quantify reactive aggression in BPD. Therefore, clinicians and researchers might consider this task, as a short experimental measure of reactive aggression, either in future studies or to aid diagnostic assessment during clinical practice. PMID:27851804

Gamma irradiation induces acetylcholine-evoked, endothelium-independent relaxation and activatesk-channels of isolated pulmonary artery of rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eder, Veronique; Gautier, Mathieu; Boissiere, Julien

2004-12-01

Purpose: To test the effects of irradiation (R*) on the pulmonary artery (PA). Methods and materials: Isolated PA rings were submitted to gamma irradiation (cesium, 8 Gy/min{sup -1}) at doses of 20 Gy-140 Gy. Rings were placed in an organ chamber, contracted with serotonin (10{sup -4} M 5-hydroxytryptamine [5-HT]), then exposed to acetylcholine (ACh) in incremental concentrations. Smooth muscle cell (SMC) membrane potential was measured with microelectrodes. Results: A high dose of irradiation (60 Gy) increased 5HT contraction by 20%, whereas lower (20 Gy) doses slightly decreased it compared with control. In the absence of the endothelium, 5-HT precontracted ringsmore » exposed to 20 Gy irradiation developed a dose-dependent relaxation induced by acetylcholine (EI-ACh) with maximal relaxation of 60 {+-} 17% (n = 13). This was totally blocked by L-NAME (10{sup -4} M), partly by 7-nitro indazole; it was abolished by hypoxia and iberiotoxin, decreased by tetra-ethyl-ammonium, and not affected by free radical scavengers. In irradiated rings, hypoxia induced a slight contraction which was never observed in control rings. No differences in SMC membrane potential were observed between irradiated and nonirradiated PA rings. Conclusion: Irradiation mediates endothelium independent relaxation by a mechanism involving the nitric oxide pathway and K-channels.« less

Acetylcholine contributes to the integration of self-movement cues in head direction cells.

PubMed

Yoder, Ryan M; Chan, Jeremy H M; Taube, Jeffrey S

2017-08-01

Acetylcholine contributes to accurate performance on some navigational tasks, but details of its contribution to the underlying brain signals are not fully understood. The medial septal area provides widespread cholinergic input to various brain regions, but selective damage to medial septal cholinergic neurons generally has little effect on landmark-based navigation, or the underlying neural representations of location and directional heading in visual environments. In contrast, the loss of medial septal cholinergic neurons disrupts navigation based on path integration, but no studies have tested whether these path integration deficits are associated with disrupted head direction (HD) cell activity. Therefore, we evaluated HD cell responses to visual cue rotations in a familiar arena, and during navigation between familiar and novel arenas, after muscarinic receptor blockade with systemic atropine. Atropine treatment reduced the peak firing rate of HD cells, but failed to significantly affect other HD cell firing properties. Atropine also failed to significantly disrupt the dominant landmark control of the HD signal, even though we used a procedure that challenged this landmark control. In contrast, atropine disrupted HD cell stability during navigation between familiar and novel arenas, where path integration normally maintains a consistent HD cell signal across arenas. These results suggest that acetylcholine contributes to path integration, in part, by facilitating the use of idiothetic cues to maintain a consistent representation of directional heading. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Altered neurogenic and mechanical responses to acetylcholine, ATP and substance P in detrusor from rat with outlet obstruction.

PubMed

Pinna, C; Sanvito, P; Puglisi, L

2006-08-22

The well-known side effects of anticholinergic compounds used to treat urinary incontinence caused by detrusor overactivity have addressed the interest on other pharmacological intervention. The purpose of the present work was to investigate the possible changes in purinergic and cholinergic components of parasympathetic neurotransmission in obstructed rat bladders with detrusor overactivity, and to examine the effect of the association of suramin, atropine and indomethacin on nerve-mediated responses to electrical field stimulation (EFS). Mechanical responses to exogenous acetylcholine, ATP and substance P were also evaluated. Altered sensitivities to acetylcholine and to the sensory neurotransmitter substance P, but unchanged sensitivity to the stable ATP analogue alpha,beta-methyleneATP were observed in bladders from obstructed rats. Suramin and atropine inhibited purinergic and cholinergic components of the neurogenic responses evoked by EFS in detrusor strips from control and obstructed rats. Interestingly, suramin enhanced the antagonistic effect of atropine on neurogenic responses of detrusor strips at all frequencies of stimulation tested. Our results suggest that the association between an antimuscarinic drug and an antagonist of P2X purinoceptors such as suramin might be helpful to reduce the therapeutic dosage of the antimuscarinic drug, along with its side effects. This approach may be of interest in the therapy of patients with bladder incontinence caused by detrusor overactivity, which do not even respond to a maximal dosage of antimuscarinic drug.

Pacifists and Revenge-Seekers in Response to Unambiguous Peer Provocation.

PubMed

McDonald, Kristina L; Asher, Steven R

2018-01-19

In order to better understand why some children retaliate when they feel provoked and others do not, the present study identified "pacifistically-oriented" children who made negative interpretations in response to unambiguous provocations, yet did not endorse revenge goals, and compared them to "revenge-seeking" children who also made negative interpretations but did endorse revenge goals. Groups were identified based on seventh graders' (N = 367; 54.77% male; 22.89% racial/ethnic minority) responses to hypothetical situations in which a peer excluded and insulted them. Comparing these groups revealed that Pacifists endorsed relationship-maintaining goals and emotion regulation goals more highly than Revenge-Seekers. Revenge-Seekers reported more anger and endorsed beliefs about negative reciprocity and aggression being legitimate more highly than Pacifists. Additionally, Revenge-Seekers were more disrespect sensitive than were Pacifists, based on a measure of vigilance for signs of disrespect and expectations that others would disrespect them. Together these findings point to social-cognitive and emotion-related processes that may inhibit revenge-seeking in unambiguous provocation situations, even when children interpret the peer's behavior quite negatively.

Use of Provocative Angiography to Localize Site in Recurrent Gastrointestinal Bleeding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnston, Ciaran, E-mail: ciaranjohnston@yahoo.co.uk; Tuite, David; Pritchard, Ruth

2007-09-15

Background. While the source of most cases of lower gastrointestinal bleeding may be diagnosed with modern radiological and endoscopic techniques, approximately 5% of patients remain who have negative endoscopic and radiological investigations.Clinical Problem. These patients require repeated hospital admissions and blood transfusions, and may proceed to exploratory laparotomy and intraoperative endoscopy. The personal and financial costs are significant. Method of Diagnosis and Decision Making. The technique of adding pharmacologic agents (anticoagulants, vasodilators, fibrinolytics) during standard angiographic protocols to induce a prohemorrhagic state is termed provocative angiography. It is best employed when significant bleeding would otherwise necessitate emergency surgery. Treatment. Thismore » practice frequently identifies a bleeding source (reported success rates range from 29 to 80%), which may then be treated at the same session. We report the case of a patient with chronic lower gastrointestinal hemorrhage with consistently negative endoscopic and radiological workup, who had an occult source of bleeding identified only after a provocative angiographic protocol was instituted, and who underwent succeeding therapeutic coil embolization of the bleeding vessel.« less

Interrelations of Justice, Rejection, Provocation, and Moral Disgust Sensitivity and Their Links with the Hostile Attribution Bias, Trait Anger, and Aggression

PubMed Central

Bondü, Rebecca; Richter, Philipp

2016-01-01

Several personality dispositions with common features capturing sensitivities to negative social cues have recently been introduced into psychological research. To date, however, little is known about their interrelations, their conjoint effects on behavior, or their interplay with other risk factors. We asked N = 349 adults from Germany to rate their justice, rejection, moral disgust, and provocation sensitivity, hostile attribution bias, trait anger, and forms and functions of aggression. The sensitivity measures were mostly positively correlated; particularly those with an egoistic focus, such as victim justice, rejection, and provocation sensitivity, hostile attributions and trait anger as well as those with an altruistic focus, such as observer justice, perpetrator justice, and moral disgust sensitivity. The sensitivity measures had independent and differential effects on forms and functions of aggression when considered simultaneously and when controlling for hostile attributions and anger. They could not be integrated into a single factor of interpersonal sensitivity or reduced to other well-known risk factors for aggression. The sensitivity measures, therefore, require consideration in predicting and preventing aggression. PMID:27303351

Muscarinic receptor immunoreactivity in the superior salivatory nucleus neurons innervating the salivary glands of the rat.

PubMed

Ueda, Hirotaka; Mitoh, Yoshihiro; Fujita, Masako; Kobashi, Motoi; Yamashiro, Takashi; Sugimoto, Tomosada; Ichikawa, Hiroyuki; Matsuo, Ryuji

2011-07-15

The superior salivatory nucleus (SSN) contains preganglionic parasympathetic neurons to the submandibular and sublingual salivary glands. Cevimeline, a muscarinic acetylcholine receptor agonist, stimulates the salivary glands and is presently used as sialogogue in the treatment of dry mouth. Since cevimeline passes through the blood-brain barrier, it is also able to act on muscarinic acetylcholine receptors in the central nervous system. Our preliminary experiment using the whole-cell patch-clamp technique has shown that cevimeline excites SSN neurons in rat brain slices, suggesting that SSN neurons have muscarinic acetylcholine receptors; however, it is unclear which subtypes of muscarinic acetylcholine receptors exist in SSN neurons. In the present study, we investigated immunohistochemically muscarinic acetylcholine receptor subtypes, M1 receptor (M1R), M2R, M3R, M4R, and M5R in SSN neurons. SSN neurons innervating the salivary glands, retrogradely labeled with a fluorescent tracer from the chorda-lingual nerve, mostly expressed M3R immunoreactivity (-ir) (92.3%) but not M1R-ir. About half of such SSN neurons also showed M2R- (40.1%), M4R- (54.0%) and M5R-ir (46.0%); therefore, it is probable that SSN neurons co-express M3R-ir with at least two of the other muscarinic receptor subtypes. This is the first report to show that SSN neurons contain muscarinic acetylcholine receptors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Acetylcholine and the alpha 7 nicotinic receptor: a potential therapeutic target for the treatment of periodontal disease?

PubMed Central

2013-01-01

Objectives The aim of this review is to examine the evidence for a functional cholinergic system operating within the periodontium and determine the evidence for its role in periodontal immunity. Introduction Acetylcholine can influence the immune system via the ‘cholinergic anti-inflammatory pathway’. This pathway is mediated by the vagus nerve which releases acetylcholine to interact with the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR) on proximate immuno-regulatory cells. Activation of the α7nAChR on these cells leads to down-regulated expression of pro-inflammatory mediators and thus regulates localised inflammatory responses. The role of the vagus nerve in periodontal pathophysiology is currently unknown. However, non-neuronal cells can also release acetylcholine and express the α7nAChR; these include keratinocytes, fibroblasts, T cells, B cells and macrophages. Therefore, by both autocrine and paracrine methods non-neuronal acetylcholine can also be hypothesised to modulate the localised immune response. Methods A Pubmed database search was performed for studies providing evidence for a functional cholinergic system operating in the periodontium. In addition, literature on the role of the ‘cholinergic anti-inflammatory pathway’ in modulating the immune response was extrapolated to hypothesise that similar mechanisms of immune regulation occur within the periodontium. Conclusion The evidence suggests a functional nonneuronal ‘cholinergic anti-inflammatory pathway’ may operate in the periodontium and that this may be targeted therapeutically to treat periodontal disease. PMID:22777144

Identification of the Muscarinic Acetylcholine Receptor Subtype Mediating Cholinergic Vasodilation in Murine Retinal Arterioles

PubMed Central

Sniatecki, Jan J.; Goloborodko, Evgeny; Steege, Andreas; Zavaritskaya, Olga; Vetter, Jan M.; Grus, Franz H.; Patzak, Andreas; Wess, Jürgen; Pfeiffer, Norbert

2011-01-01

Purpose. To identify the muscarinic acetylcholine receptor subtype that mediates cholinergic vasodilation in murine retinal arterioles. Methods. Muscarinic receptor gene expression was determined in murine retinal arterioles using real-time PCR. To assess the functional relevance of muscarinic receptors for mediating vascular responses, retinal vascular preparations from muscarinic receptor–deficient mice were studied in vitro. Changes in luminal arteriole diameter in response to muscarinic and nonmuscarinic vasoactive substances were measured by video microscopy. Results. Only mRNA for the M3 receptor was detected in retinal arterioles. Thus, M3 receptor–deficient mice (M3R−/−) and respective wild-type controls were used for functional studies. Acetylcholine concentration-dependently dilated retinal arterioles from wild-type mice. In contrast, vasodilation to acetylcholine was almost completely abolished in retinal arterioles from M3R−/− mice, whereas responses to the nitric oxide (NO) donor nitroprusside were retained. Carbachol, an acetylcholinesterase-resistant analog of acetylcholine, also evoked dilation in retinal arterioles from wild-type, but not from M3R−/−, mice. Vasodilation responses from wild-type mice to acetylcholine were negligible after incubation with the non–subtype-selective muscarinic receptor blocker atropine or the NO synthase inhibitor Nω-nitro-l-arginine methyl ester, and were even reversed to contraction after endothelial damage with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. Conclusions. These findings provide evidence that endothelial M3 receptors mediate cholinergic vasodilation in murine retinal arterioles via activation of NO synthase. PMID:21873683

Deletion of muscarinic type 1 acetylcholine receptors alters splenic lymphocyte functions and splenic noradrenaline concentration.

PubMed

Hainke, Susanne; Wildmann, Johannes; Del Rey, Adriana

2015-11-01

The existence of interactions between the immune and the sympathetic nervous systems is well established. Noradrenaline can promote or inhibit the immune response, and conversely, the immune response itself can affect noradrenaline concentration in lymphoid organs, such as the spleen. It is also well known that acetylcholine released by pre-ganglionic neurons can modulate noradrenaline release by the postsynaptic neuron. The spleen does not receive cholinergic innervation, but it has been reported that lymphocytes themselves can produce acetylcholine, and express acetylcholine receptors and acetylcholinesterase. We found that the spleen of not overtly immunized mice in which muscarinic type 1 acetylcholine receptors have been knocked out (M1KO) has higher noradrenaline concentrations than that of the wildtype mice, without comparable alterations in the heart, in parallel to a decreased number of IgG-producing B cells. Splenic lymphocytes from M1KO mice displayed increased in vitro-induced cytotoxicity, and this was observed only when CD4(+) T cells were present. In contrast, heterozygous acetylcholinesterase (AChE+/-) mice, had no alterations in splenic noradrenaline concentration, but the in vitro proliferation of AChE+/- CD4(+) T cells was increased. It is theoretically conceivable that reciprocal effects between neuronally and non-neuronally derived acetylcholine and noradrenaline might contribute to the results reported. Our results emphasize the need to consider the balance between the effects of these mediators for the final immunoregulatory outcome. Copyright © 2015 Elsevier B.V. All rights reserved.

Activation of α7 nicotinic acetylcholine receptors persistently enhances hippocampal synaptic transmission and prevents Aß-mediated inhibition of LTP in the rat hippocampus.

PubMed

Ondrejcak, Tomas; Wang, Qinwen; Kew, James N C; Virley, David J; Upton, Neil; Anwyl, Roger; Rowan, Michael J

2012-02-29

Nicotinic acetylcholine receptors mediate fast cholinergic modulation of glutamatergic transmission and synaptic plasticity. Here we investigated the effects of subtype selective activation of the α7 nicotinic acetylcholine receptors on hippocampal transmission and the inhibition of synaptic long-term potentiation by the Alzheimer's disease associated amyloid ß-protein (Aß). The α7 nicotinic acetylcholine receptor agonist "compound A" ((R)-N-(1-azabicyclo[2.2.2]oct-3-yl)(5-(2-pyridyl))thiophene-2-carboxamide) induced a rapid-onset persistent enhancement of synaptic transmission in the dentate gyrus in vitro. Consistent with a requirement for activation of α7 nicotinic acetylcholine receptors, the type II α7-selective positive allosteric modulator PheTQS ((3aR, 4S, 9bS)-4-(4-methylphenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide) potentiated, and the antagonist methyllycaconitine (MLA) prevented the persistent enhancement. Systemic injection of the agonist also induced a similar MLA-sensitive persistent enhancement of synaptic transmission in the CA1 area in vivo. Remarkably, although compound A did not affect control long-term potentiation (LTP) in vitro, it prevented the inhibition of LTP by Aß1-42 and this effect was inhibited by MLA. These findings strongly indicate that activation of α7 nicotinic acetylcholine receptors is sufficient to persistently enhance hippocampal synaptic transmission and to overcome the inhibition of LTP by Aß. Copyright © 2011 Elsevier B.V. All rights reserved.

Allosteric modulation of alpha4beta2 nicotinic acetylcholine receptors by HEPES✩

PubMed Central

Weltzin, Maegan M; Huang, Yanzhou; Schulte, Marvin K

2013-01-01

A number of new positive allosteric modulators (PAMs) have been reported that enhance responses of neuronal alpha7 and alpha4beta2 nicotinic acetylcholine receptor subtypes to orthosteric ligands. PAMs represent promising new leads for the development of therapeutic agents for disorders involving alterations in nicotinic neurotransmission including Autism, Alzheimer's and Parkinson's disease. During our recent studies of alpha4beta2 PAMs, we identified a novel effect of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). The effects of HEPES were evaluated in a phosphate buffered recording solution using two-electrode voltage clamp techniques and alpha4beta2 and alpha7 nicotinic acetylcholine receptor subtypes expressed in Xenopus laevis oocytes. Acetylcholine induced responses of high-sensitivity alpha4beta2 receptors were potentiated 190% by co-exposure to HEPES. Responses were inhibited at higher concentrations (bell-shaped concentration/response curve). Coincidentally, at concentrations of HEPES typically used in oocyte recording (5–10 mM), the potentiating effects of HEPES are matched by its inhibitory effects, thus producing no net effect. Mutagenesis results suggest HEPES potentiates the high-sensitivity stoichiometry of the alpha4beta2 receptors through action at the beta2+/beta2− interface and is dependent on residue beta2D218. HEPES did not potentiate low-sensitivity alpha4beta2 receptors and did not produce any observable effect on acetylcholine induced responses on alpha7 nicotinic acetylcholine receptors. PMID:22732654

Allosteric modulation of alpha4beta2 nicotinic acetylcholine receptors by HEPES.

PubMed

Weltzin, Maegan M; Huang, Yanzhou; Schulte, Marvin K

2014-06-05

A number of new positive allosteric modulators (PAMs) have been reported that enhance responses of neuronal alpha7 and alpha4beta2 nicotinic acetylcholine receptor subtypes to orthosteric ligands. PAMs represent promising new leads for the development of therapeutic agents for disorders involving alterations in nicotinic neurotransmission including Autism, Alzheimer's and Parkinson's disease. During our recent studies of alpha4beta2 PAMs, we identified a novel effect of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). The effects of HEPES were evaluated in a phosphate buffered recording solution using two-electrode voltage clamp techniques and alpha4beta2 and alpha7 nicotinic acetylcholine receptor subtypes expressed in Xenopus laevis oocytes. Acetylcholine induced responses of high-sensitivity alpha4beta2 receptors were potentiated 190% by co-exposure to HEPES. Responses were inhibited at higher concentrations (bell-shaped concentration/response curve). Coincidentally, at concentrations of HEPES typically used in oocyte recording (5-10mM), the potentiating effects of HEPES are matched by its inhibitory effects, thus producing no net effect. Mutagenesis results suggest HEPES potentiates the high-sensitivity stoichiometry of the alpha4beta2 receptors through action at the beta2+/beta2- interface and is dependent on residue beta2D218. HEPES did not potentiate low-sensitivity alpha4beta2 receptors and did not produce any observable effect on acetylcholine induced responses on alpha7 nicotinic acetylcholine receptors. Copyright © 2012 Elsevier B.V. All rights reserved.

Cholinergic Overstimulation Attenuates Rule Selectivity in Macaque Prefrontal Cortex.

PubMed

Major, Alex J; Vijayraghavan, Susheel; Everling, Stefan

2018-01-31

Acetylcholine is released in the prefrontal cortex (PFC) and is a key modulator of cognitive performance in primates. Cholinergic stimulation has been shown to have beneficial effects on performance of cognitive tasks, and cholinergic receptors are being actively explored as promising targets for ameliorating cognitive deficits in Alzheimer's disease. We hypothesized that cholinergic stimulation of PFC during performance of a cognitive task would augment neuronal activity and neuronal coding of task attributes. We iontophoretically applied the general cholinergic receptor agonist carbachol onto neurons in dorsolateral PFC (DLPFC) of male rhesus macaques performing rule-guided prosaccades and antisaccades, a well established oculomotor task for testing cognitive control. Carbachol application had heterogeneous effects on neuronal excitability, with both excitation and suppression observed in significant proportions. Contrary to our prediction, neurons with rule-selective activity exhibited a reduction in selectivity during carbachol application. Cholinergic stimulation disrupted rule selectivity regardless of whether it had suppressive or excitatory effects on these neurons. In addition, cholinergic stimulation excited putative pyramidal neurons, whereas the activity of putative interneurons remained unchanged. Moreover, cholinergic stimulation attenuated saccade direction selectivity in putative pyramidal neurons due to nonspecific increases in activity. Our results suggest excessive cholinergic stimulation has detrimental effects on DLPFC representations of task attributes. These findings delineate the complexity and heterogeneity of neuromodulation of cerebral cortex by cholinergic stimulation, an area of active exploration with respect to the development of cognitive enhancers. SIGNIFICANCE STATEMENT The neurotransmitter acetylcholine is known to be important for cognitive processes in the prefrontal cortex. Removal of acetylcholine from prefrontal cortex can disrupt short-term memory performance and is reminiscent of Alzheimer's disease, which is characterized by degeneration of acetylcholine-producing neurons. Stimulation of cholinergic receptors is being explored to create cognitive enhancers for the treatment of Alzheimer's disease and other psychiatric diseases. Here, we stimulated cholinergic receptors in prefrontal cortex and examined its effects on neurons that are engaged in cognitive behavior. Surprisingly, cholinergic stimulation decreased neurons' ability to discriminate between rules. This work suggests that overstimulation of acetylcholine receptors could disrupt neuronal processing during cognition and is relevant to the design of cognitive enhancers based on stimulating the cholinergic system. Copyright © 2018 the authors 0270-6474/18/381137-14$15.00/0.

Amperometric determination of acetylcholine-A neurotransmitter, by chitosan/gold-coated ferric oxide nanoparticles modified gold electrode.

PubMed

Chauhan, Nidhi; Pundir, C S

2014-11-15

An amperometric acetylcholine biosensor was constructed by co-immobilizing covalently, a mixture of acetylcholinesterase (AChE) and choline oxidase (ChO) onto nanocomposite of chitosan (CHIT)/gold-coated ferric oxide nanoparticles (Fe@AuNPs) electrodeposited onto surface of a Au electrode and using it as a working electrode, Ag/AgCl as reference electrode and Pt wire as auxiliary electrode connected through potentiostat. The biosensor is based on electrochemical measurement of H2O2 generated from oxidation of choline by immobilized ChO, which in turn is produced from hydrolysis of acetylcholine by immobilized AChE. The biosensor exhibited optimum response within 3s at +0.2V, pH 7.0 and 30°C. The enzyme electrode had a linear working range of 0.005-400 µM, with a detection limit of 0.005 µM for acetylcholine. The biosensor measured plasma acetylcholine in apparently healthy and persons suffering from Alzheimer's disease. The enzyme electrode was unaffected by a number of serum substances but lost 50% of its initial activity after its 100 uses over a period of 3 months, when stored at 4°C. Copyright © 2014 Elsevier B.V. All rights reserved.

Theoretical investigation of interaction between the set of ligands and α7 nicotinic acetylcholine receptor

NASA Astrophysics Data System (ADS)

Glukhova, O. E.; Prytkova, T. R.; Shmygin, D. S.

2016-03-01

Nicotinic acetylcholine receptors (nAChRs) are neuron receptor proteins that provide a transmission of nerve impulse through the synapses. They are composed of a pentametric assembly of five homologous subunits (5 α7 subunits for α7nAChR, for example), oriented around the central pore. These receptors might be found in the chemical synapses of central and peripheral nervous system, and also in the neuromuscular synapses. Transmembrane domain of the one of such receptors constitutes ion channel. The conductive properties of ion channel strongly depend on the receptor conformation changes in the response of binding with some molecule, f.e. acetylcholine. Investigation of interaction between ligands and acetylcholine receptor is important for drug design. In this work we investigate theoretically the interaction between the set of different ligands (such as vanillin, thymoquinone, etc.) and the nicotinic acetylcholine receptor (primarily with subunit of the α7nAChR) by different methods and packages (AutodockVina, GROMACS, KVAZAR, HARLEM, VMD). We calculate interaction energy between different ligands in the subunit using molecular dynamics. On the base of obtained calculation results and using molecular docking we found an optimal location of different ligands in the subunit.

Oxotremorine suppresses thalamocortical oscillations via thalamic muscarinic acetylcholine receptors.

PubMed

Puoliväli, J; Jäkälä, P; Koivisto, E; Riekkinen, P

1998-12-01

We investigated whether the local intrathalamic infusion of a muscarinic acetylcholine receptor agonist (oxotremorine) at either the reticular nucleus of thalamus (NRT) or the ventroposteromedial nucleus of thalamus (VPM) suppresses thalamocortically generated neocortical high-voltage spindles (HVSs). In addition, we studied whether the intracerebroventricular (ICV) infusion of a selective muscarinic M2 acetylcholine receptor antagonist (methoctramine) could block the suppression of HVSs induced by either systemic (IP) administration of an anticholinesterase drug [tetrahydroaminoacridine (THA)] or ICV infusion of oxotremorine in rats. Intrathalamic administration of oxotremorine at 3 and 15 microg in the NRT, and at 15 microg in the VPM suppressed HVSs. ICV oxotremorine at 30 and 100 microg and IP THA at 3 mg/kg decreased HVSs. ICV methoctramine at 100 microg increased HVSs and completely blocked the decrease in HVSs produced by oxotremorine 100 microg and THA 3 mg/kg. The results suggest that activation of muscarinic M2 acetylcholine receptors in thalamic nuclei (NRT and VPM) can suppress thalamocortical oscillations and that ICV or systemically administered drugs that activate either directly (oxotremorine and methoctramine) or indirectly (THA) the muscarinic M2 acetylcholine receptors may modulate neocortical HVSs via the thalamus.

Preliminary criteria for the definition of allergic rhinitis: a systematic evaluation of clinical parameters in a disease cohort (I).

PubMed

Ng, M L; Warlow, R S; Chrishanthan, N; Ellis, C; Walls, R

2000-09-01

The aim of this study is to formulate criteria for the definition of allergic rhinitis. Other studies have sought to develop scoring systems to categorize the severity of allergic rhinitis symptoms but it was never used for the formulation of diagnostic criteria. These other scoring systems were arbitrarily chosen and were not derived by any statistical analysis. To date, a study of this kind has not been performed. The hypothesis of this study is that it is possible to formulate criteria for the definition of allergic rhinitis. This is the first study to systematically examine and evaluate the relative importance of symptoms, signs and investigative tests in allergic rhinitis. We sought to statistically rank, from the most to the least important, the multiplicity of symptoms, signs and test results. Forty-seven allergic rhinitis and 23 normal subjects were evaluated with a detailed questionnaire and history, physical examination, serum total immunoglobulin E, skin prick tests and serum enzyme allergosorbent tests (EAST). Statistical ranking of variables indicated rhinitis symptoms (nasal, ocular and oronasal) were the most commonly occurring, followed by a history of allergen provocation, then serum total IgE, positive skin prick tests and positive EAST's to house dust mite, perennial rye and bermuda/couch grass. Throat symptoms ranked even lower whilst EAST's to cat epithelia, plantain and cockroach were the least important. Not all symptoms, signs and tests evaluated proved to be statistically significant when compared to a control group; this included symtoms and signs which had been considered historically to be traditionally associated with allergic rhinitis, e.g. sore throat and bleeding nose. In performing statistical analyses, we were able to rank from most to least important, the multiplicity of symptoms signs and test results. The most important symptoms and signs were identified for the first time, even though some of these were not included in our original selection criteria for defining the disease cohort i.e. sniffing, postnasal drip, oedematous nasal mucosa, impaired sense of smell, mouth breathing, itchy nose and many of the specific provocation factors.

Validation of the Novaco Anger Scale-Provocation Inventory (Danish) With Nonclinical, Clinical, and Offender Samples.

PubMed

Moeller, Stine Bjerrum; Novaco, Raymond W; Heinola-Nielsen, Vivian; Hougaard, Helle

2016-10-01

Anger has high prevalence in clinical and forensic settings, and it is associated with aggressive behavior and ward atmosphere on psychiatric units. Dysregulated anger is a clinical problem in Danish mental health care systems, but no anger assessment instruments have been validated in Danish. Because the Novaco Anger Scale and Provocation Inventory (NAS-PI) has been extensively validated with different clinical populations and lends itself to clinical case formulation, it was selected for translation and evaluation in the present multistudy project. Psychometric properties of the NAS-PI were investigated with samples of 477 nonclinical, 250 clinical, 167 male prisoner, and 64 male forensic participants. Anger prevalence and its relationship with other anger measures, anxiety/depression, and aggression were examined. NAS-PI was found to have high reliability, concurrent validity, and discriminant validity, and its scores discriminated the samples. High scores in the offender group demonstrated the feasibility of obtaining self-report assessments of anger with this population. Retrospective and prospective validity of the NAS were tested with the forensic patient sample regarding physically aggressive behavior in hospital. Regression analyses showed that higher scores on NAS increase the risk of having acted aggressively in the past and of acting aggressively in the future. © The Author(s) 2015.

PCR analysis of a prescription vegetarian diet and use in three dogs with cutaneous adverse food reactions.

PubMed

Aufox, Erin E; May, Elizabeth R; Frank, Linda A; Kania, Stephen A

2018-04-24

Cutaneous adverse food reaction (CAFR) is diagnosed by performing an elimination diet trial utilizing prescription or home-cooked diets followed by provocative challenge. To report findings of PCR analysis of a prescription vegetarian diet (RCV) for undeclared proteins of animal origin, as well as to describe its utilization for diagnosis and management of dogs suspected of having CAFR. Three client-owned dogs. PCR analysis of RCV for 11 mammalian species and poultry. In three dogs, clinical examination, cytology, aerobic culture (if indicated) and at least one elimination diet trial with RCV. In our case series, all dogs had a history of pruritus and recurrent pyoderma that resolved with infection control and an elimination diet trial. In cases 1 and 2, a diagnosis of CAFR was made following an elimination trial with RCV and provocative challenge. Case 3 had a previously confirmed diagnosis of CAFR and RCV was successfully used to maintain remission of CAFR-related signs. PCR testing of RCV was negative for 11 mammalian species and poultry. The RCV diet was found not to contain any undeclared mammalian or avian proteins. In this case series, the RCV was successfully used to diagnose and maintain three dogs with CAFR. © 2018 ESVD and ACVD.

Repetitive transcranial magnetic stimulation modulates the impact of a negative mood induction.

PubMed

Möbius, Martin; Lacomblé, Lylis; Meyer, Thomas; Schutter, Dennis J L G; Gielkens, Tom; Becker, Eni S; Tendolkar, Indira; van Eijndhoven, Philip

2017-04-01

High frequency repetitive Transcranial Magnetic Stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been found to alleviate depressive symptoms. However, the mechanisms driving these effects are still poorly understood. In the current study, we tested the idea that this intervention protects against negative mood shifts following emotional provocation. We furthermore explored changes in EEG activity (frontal alpha asymmetry) and effects on attentional processing (emotional Stroop). To this end, 23 healthy individuals participated in two sessions separated by one week, whereby they once received 15 min of 10Hz rTMS stimulation (1500 pulses) at 110% of the individual motor threshold, and once sham stimulation. Then, negative mood was induced using sad movie clips. The results revealed a significantly stronger mood decline following rTMS compared to sham stimulation. No changes were observed in frontal alpha asymmetry and attentional processing. Our findings are at odds with the view that high frequency rTMS over the left DLPFC directly protects against the induction of negative mood, but rather suggest that it enhances the effects of emotional provocation. Possibly, in healthy young individuals, this stimulation protocol heightens susceptibility to mood induction procedures in general. © The Author (2016). Published by Oxford University Press.

Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis: double blind randomised controlled study.

PubMed

Radcliffe, Michael J; Lewith, George T; Turner, Richard G; Prescott, Philip; Church, Martin K; Holgate, Stephen T

2003-08-02

To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy. Double blind randomised placebo controlled parallel group study. Hospital in Hampshire. 183 participants aged between 18 and 64 with a history of severe summer hay fever for at least two years; all were skin prick test positive to timothy grass pollen. 90 randomised to active treatment; 93 randomised to placebo. Active treatment: two injections of enzyme potentiated desensitisation, given between eight and 11 weeks apart, each comprising 200 Fishman units of beta glucuronidase, 50 pg 1,3-cyclohexanediol, 50 ng protamine sulphate, and a mixed inhaled allergen extract (pollen mixes for trees, grasses, and weeds; allergenic fungal spores; cat and dog danders; dust and storage mites) in a total volume of 0.05 ml of buffered saline. Placebo: two injections of 0.05 ml buffered saline solution. Proportion of problem-free days; global rhinoconjunctivitis quality of life scores assessed weekly during pollen season. The active treatment group and the placebo group did not differ in the proportion of problem-free days, quality of life scores, symptom severity scores, change in quantitative skin prick provocation threshold, or change in conjunctival provocation threshold. No clinically significant adverse reactions occurred. Enzyme potentiated desensitisation showed no treatment effect in this study.

Hallermann-Streiff syndrome with hypopituitarism contributing to growth failure.

PubMed

Pivnick, E K; Burstein, S; Wilroy, R S; Kaufman, R A; Ward, J C

1991-12-15

A 35-month-old black boy with Hallermann-Streiff syndrome (HSS) was evaluated for anterior hypopituitarism when he presented with ketotic hypoglycemia, microgenitalia, and short stature. Endocrine evaluation showed a low T4 and TSH levels, suggesting hypothalamic hypothyroidism; this was confirmed by TRH stimulation. Metyrapone test confirmed ACTH deficiency as a contributing factor to the ketotic hypoglycemia. A superagonist GnRH test suggested hypothalamic GnRH deficiency. Growth hormone provocative testing conclusively demonstrated complete growth hormone deficiency. MRI investigation of the brain suggested hypopituitarism. Although facial findings were not completely classical of the HSS, we suggest these may be somewhat altered due to his racial back-ground. We recommend endocrine evaluation of HSS patients with manifestations suggesting hypopituitarism since treatment of this condition will improve the quality of life of these patients.

Prefrontal cortex, caloric restriction and stress during aging: studies on dopamine and acetylcholine release, BDNF and working memory.

PubMed

Del Arco, Alberto; Segovia, Gregorio; de Blas, Marta; Garrido, Pedro; Acuña-Castroviejo, Dario; Pamplona, Reinald; Mora, Francisco

2011-01-01

This study was designed to investigate whether long-term caloric restriction during the life span of the rat changes the effects of an acute mild stress on the release of dopamine and acetylcholine in the prefrontal cortex (PFC) and on working memory performance. Spontaneous motor activity was also monitored and levels of BDNF measured in the prefrontal cortex, amygdala and hippocampus. Male Wistar rats (3 months of age) were housed during 3, 12, 21 and 27 months (6, 15, 24 and 30 months of age at the end of housing) in caloric restriction (CR; 40% food intake restriction) or control conditions. After behavioural testing, animals were further subdivided into two other groups. In one of the groups BDNF protein levels were determined. In the other group rats were implanted with guide cannulas into the PFC to perform microdialysis experiments. In CR rats the release of dopamine produced by handling stress did not differ from the response found in control rats of 6, 15 and 24 months of age. The release of acetylcholine was not changed at the ages of 6 and 15 months but reduced at the age of 24 months. Stress did not change dopamine or acetylcholine release in CR and control rats of 30 months of age. BDNF levels were increased in the hippocampus and amygdala, but not in the PFC, of 6 and 15 months CR rats. Spontaneous motor activity was increased in all groups of CR rats. Age, however, decreased motor activity in CR and control rats. Both experimental groups showed similar working memory performance in a delayed alternation task in basal conditions and after a situation of acute stress. These results suggest that CR does not modify the function of the PFC in response to an acute stress nor the changes found as a result of the normal process of aging. Copyright © 2010 Elsevier B.V. All rights reserved.

Computer modeling of the neurotoxin binding site of acetylcholine receptor spanning residues 185 through 196

NASA Technical Reports Server (NTRS)

Garduno-Juarez, R.; Shibata, M.; Zielinski, T. J.; Rein, R.

1987-01-01

A model of the complex between the acetylcholine receptor and the snake neurotoxin, cobratoxin, was built by molecular model building and energy optimization techniques. The experimentally identified functionally important residues of cobratoxin and the dodecapeptide corresponding to the residues 185-196 of acetylcholine receptor alpha subunit were used to build the model. Both cis and trans conformers of cyclic L-cystine portion of the dodecapeptide were examined. Binding residues independently identified on cobratoxin are shown to interact with the dodecapeptide AChR model.