Diverse mechanisms underlying the regulation of ion channels by carbon monoxide

Carbon monoxide (CO) is firmly established as an important, physiological signalling molecule as well as a potent toxin. Through its ability to bind metal-containing proteins, it is known to interfere with a number of intracellular signalling pathways, and such actions can account for its physiological and pathological effects. In particular, CO can modulate the intracellular production of reactive oxygen species, NO and cGMP levels, as well as regulate MAPK signalling. In this review, we consider ion channels as more recently discovered effectors of CO signalling. CO is now known to regulate a growing number of different ion channel types, and detailed studies of the underlying mechanisms of action are revealing unexpected findings. For example, there are clear areas of contention surrounding its ability to increase the activity of high conductance, Ca²⁺-sensitive K⁺ channels. More recent studies have revealed the ability of CO to inhibit T-type Ca²⁺ channels and have unveiled a novel signalling pathway underlying tonic regulation of this channel. It is clear that the investigation of ion channels as effectors of CO signalling is in its infancy, and much more work is required to fully understand both the physiological and the toxic actions of this gas. Only then can its emerging use as a therapeutic tool be fully and safely exploited.

Linked Articles

This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6     

Artificial intelligence in gastroenterology: A state-of-the-art review

The development of artificial intelligence (AI) has increased dramatically in the last 20 years, with clinical applications progressively being explored for most of the medical specialties. The field of gastroenterology and hepatology, substantially reliant on vast amounts of imaging studies, is not an exception. The clinical applications of AI systems in this field include the identification of premalignant or malignant lesions (e.g., identification of dysplasia or esophageal adenocarcinoma in Barrett’s esophagus, pancreatic malignancies), detection of lesions (e.g., polyp identification and classification, small-bowel bleeding lesion on capsule endoscopy, pancreatic cystic lesions), development of objective scoring systems for risk stratification, predicting disease prognosis or treatment response [e.g., determining survival in patients post-resection of hepatocellular carcinoma), determining which patients with inflammatory bowel disease (IBD) will benefit from biologic therapy], or evaluation of metrics such as bowel preparation score or quality of endoscopic examination. The objective of this comprehensive review is to analyze the available AI-related studies pertaining to the entirety of the gastrointestinal tract, including the upper, middle and lower tracts; IBD; the hepatobiliary system; and the pancreas, discussing the findings and clinical applications, as well as outlining the current limitations and future directions in this field.     

Magnetic field interactions between current consumer electronics and cardiac implantable electronic devices

Journal of Interventional Cardiac Electrophysiology - Ablation index (AI) is a radiofrequency lesion quality marker. The AI value that allows effective and safe pulmonary vein isolation (PVI) is...     

Oxygen cost of exercise is increased in heart failure after accounting for recovery costs

STUDY OBJECTIVES: The oxygen cost during exercise has been reported to be decreased in patients with congestive heart failure (CHF), implying an increased efficiency (lower oxygen uptake [VO(2)] per Watt [VO(2)/W]); however, these studies ignored the oxygen debt that is increased in heart failure. SUBJECTS: The primary aim of this research was to evaluate the total oxygen cost (work VO(2)/W) during exercise and recovery in patients with heart failure as compared with healthy adults. DESIGN AND PATIENTS: We performed a retrospective analysis comparing the exercise VO(2)/W, the recovery VO(2)/W, the work VO(2)/W, and the VO(2)/W relationship above and below the ventilatory threshold (VT) in 11 healthy control subjects and 45 patients with CHF. RESULTS: The exercise VO(2)/W was decreased by 29% (p < 0.0001) in patients with CHF; however, the recovery VO(2)/W was increased by 167% (p < 0.0001) and the work VO(2)/W was increased by 14% in patients with CHF (p = 0.014). The VO(2)/W slope increased above the VT (+ 27%, p = 0.0017) in both normal subjects and patients with CHF, suggesting a decrease in efficiency above the VT. There was an inverse correlation (r = 0.646, p < 0.0001) between exercise VO(2)/W and recovery VO(2)/W, implying that subjects with a low exercise VO(2)/W were not efficient but rather accumulated a large oxygen debt that was repaid following completion of exercise. CONCLUSIONS: Heart failure is associated with lower exercise VO(2)/W; however, the patient with heart failure is not efficient, but rather accumulating a large oxygen debt (recovery VO(2)/W) that is repaid following exercise. In addition, the work VO(2)/W (including both exercise and recovery) is increased in patients with heart failure in comparison to control subjects, and correlates inversely with the percentage of predicted VO(2). The large recovery VO(2)/W is likely due to impaired oxygen delivery to exercising muscle during exercise. The increase in the work VO(2)/W is probably due to changes in skeletal muscle fiber type that occur in patients with heart failure (type I to type IIb).     

Isosorbide dinitrate and intra-aortic balloon pumping in preinfarctional angina. Effects on central circulatory dynamics.

The dynamics of the central circulation were measured by a radionuclidic technique in 18 men with high-risk preinfarctional angina who received therapy with isosorbide dinitrate (n equals 18), intra-aortic balloon pumping (n equals 8), or both (n equals 8). Administration of 5 mg of isosorbide dinitrate sublinqually was associated with a reduction in stroke volume index (SVI), cardiac index (CI), systemic arterial blood pressure, and left ventricular end-diastolic volume (LVEDV) and with increased left ventricular ejection fraction (LVEF). Intra-aortic balloon pumping did not alter SVI or CI, but decreased systolic blood pressure and LVEDV and increased LVEF and diastolic blood pressure. The combination of therapy with isosorbide dinitrate and intraaortic balloon pumping resulted in decreased SVI, systolic blood pressure, and LVEDV and increased LVEF. Thus, therapy with isosorbide dinitrate reduced left ventricular preload, and intra-aortic balloon pumping reduced blood pressure, which resulted in a decreased LVEDV and an increase in LVEF. Therapy with isosorbide dinitrate and intra-aortic balloon pumping act to alter central circulatory dynamics in favor of reducing myocardial oxygen demand.     

Clinical reporting of radiographs by radiographers: Policy and practice guidance for regional imaging networks

ObjectivesRadiographer reporting is an essential component of imaging across the United Kingdom. Since the previous policy and practice guidance in 2004 the role and contribution of reporting radiographers has changed significantly. The move to imaging networks further reinforces the need for consistency in scope of practice and clinical governance for radiographer reporting.Key findingsThis guidance provides a consistent, evidence-based template for planning a reporting service, resourcing, clinical governance, preceptorship, volume and frequency of reporting, a peer learning framework and expected standards.ConclusionDeveloped for North Central and East London, this framework and standards will help reduce unwarranted variation.Implications for practiceConsistency in practice could help maximise the contribution of radiographer reporting.     

Can attachment and peer relation constructs predict anxiety in ethnic minority youths? A longitudinal exploratory study

ABSTRACT

Anxiety is the most prevalent psychiatric disturbance in childhood effecting typically 15–20% of all youth. It has been associated with attachment insecurity and reduced competence in peer relations. Prior work has been limited by including mainly White samples, relying on questionnaires, and applying a cross-sectional design. The present study addressed these limitations by considering how at-risk non-White youth (n = 34) responded to the Friends and Family Interview (FFI) in middle childhood and how this linked up with anxiety symptoms and an anxiety diagnosis three years later in early adolescence. Five dimensions of secure attachment, namely, (i) to mother, (ii) to father, (iii) coherence, (iv) developmental understanding, and (v) social competence and quality of contact with best friend in middle childhood, were found to correlate significantly (and negatively) with self-reported anxiety symptoms. Linear regression results showed independent influences of female gender, and (low) quality of best friend contact as the most efficient model predicting anxiety symptoms. Logistic regression results suggested a model that included female gender, low social competence, and immature developmental understanding as efficient predictors of an anxiety diagnosis, evident in only 18% of the sample. These results point to the usefulness of after-school programs for at-risk minority youth in promoting peer competence, developmental awareness, and minimizing anxiety difficulties.     

Previously identified patellar tendinopathy risk factors differ between elite and sub‐elite volleyball players

Patellar tendinopathy is the most common knee injury incurred in volleyball, with its prevalence in elite athletes more than three times that of their sub‐elite counterparts. The purpose of this study was to determine whether patellar tendinopathy risk factors differed between elite and sub‐elite male volleyball players. Nine elite and nine sub‐elite male volleyball players performed a lateral stop–jump block movement. Maximum vertical jump, training history, muscle extensibility and strength, three‐dimensional landing kinematics (250 Hz), along with lower limb neuromuscular activation patterns (1500 Hz), and patellar tendon loading were collected during each trial. Multivariate analyses of variance (P < 0.05) assessed for between‐group differences in risk factors or patellar tendon loading. Significant interaction effects were further evaluated using post‐hoc univariate analysis of variance tests. Landing kinematics, neuromuscular activation patterns, patellar tendon loading, and most of the previously identified risk factors did not differ between the elite and sub‐elite players. However, elite players participated in a higher training volume and had less quadriceps extensibility than sub‐elite players. Therefore, high training volume is likely the primary contributor to the injury discrepancy between elite and sub‐elite volleyball players. Interventions designed to reduce landing frequency and improve quadriceps extensibility are recommended to reduce patellar tendinopathy prevalence in volleyball players.