Effect of l-Arginine on Human Coronary Endothelium-Dependent and Physiologic Vasodilation

AbstractObjectives. We hypothesized that l-arginine would improve abnormal coronary vasodilation in response to physiologic stress in patients with atherosclerosis and its risk factors by reversing coronary endothelial dysfunction.Background. Studies have demonstrated that physiologic coronary vasodilation correlates with endothelial function and that l-arginine, the substrate for nitric oxide synthesis, improves the response to acetylcholine (Ach).Methods. Changes in coronary blood flow and epicardial diameter response to Ach, adenosine and cardiac pacing were measured in 32 patients with coronary atherosclerosis or its risk factors and in 7 patients without risk factors and normal coronary angiograms.Results. Intracoronary l-arginine did not alter baseline coronary vascular tone, but the epicardial and microvascular responses to Ach were enhanced (both p < 0.001). The improvement after l-arginine was greater in epicardial segments that initially constricted with Ach; similarly, l-arginine abolished microvascular constriction produced by higher doses of Ach. Thus, there was a negative correlation between the initial epicardial and vascular resistance responses to Ach and the magnitude of improvement with l-arginine (r = −0.55 and r = −0.50, respectively, p < 0.001). d-Arginine did not affect the responses to Ach, and adenosine responses were unchanged with l-arginine. Cardiac pacing-induced epicardial constriction was abolished by l-arginine, but microvascular dilation remained unaffected.Conclusions. Thus, l-arginine improved endothelium-dependent coronary epicardial and microvascular function in patients with endothelial dysfunction. Prevention of epicardial constriction during physiologic stress by l-arginine in patients with endothelial dysfunction may be of therapeutic value in the treatment of myocardial ischemia

Revisiting the Prevalence of Autism Spectrum Disorder among Omani Children: A multicentre study

Objectives: This study aimed to provide an updated estimate of the prevalence of autism spectrum disorder (ASD) among Omani children. Methods: This retrospective descriptive study was conducted from December 2011 to December 2018. Data were retrieved from the three main autism diagnostic centres in Oman: Sultan Qaboos University Hospital, Royal Hospital and Al-Massarah Hospital. The ASD diagnosis was made by experienced clinicians based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The overall population prevalence estimates per 10,000 children aged 0–14 years old in Oman were calculated using the denominator of the mid-period population data. Results: A total of 1,705 ASD cases were identified with the majority of cases being male (78.1%). The overall prevalence rate of ASD was estimated at 20.35 per 10,000 children (95% confidence interval: 19.39–21.32) between 2012–2018. Boys were found to have a 3.4-fold higher prevalence of ASD than girls (31.23/10,000 versus 9.07/10,000). Regionally, the majority of cases were found in the capital, Muscat, where the highest prevalence was 36.51 cases per 10,000 children. Conclusion: The prevalence of ASD among Omani children is 15-fold higher than estimates from 2011. This increase can be attributed to improvements in diagnostic services, increased awareness of ASD, better screening programmes and changes in diagnostic criteria. In addition, this increase in prevalence suggests a need for a registry of developmental disabilities and more extensive diagnostic and rehabilitation services in Oman.Keywords: Autism Spectrum Disorder; Epidemiology; Prevalence; Oman

Antivascular therapy of human follicular thyroid cancer experimental bone metastasis by blockade of Epidermal Growth Factor Receptor and Vascular Growth Factor Receptor phosphorylation

Patients suffering from bone metastases of Follicular Thyroid Carcinoma (FTC) have a poor prognosis because of the lack of effective treatment strategies. The overexpression of Epidermal Growth Factor Receptor (EGFR) associated with increased vascularity has been implicated in the pathogenesis of FTC and subsequent bone metastases. We hypothesized that inhibiting the phosphorylation of the EGFR and Vascular Endothelial Growth Factor Receptor (VEGFR) by AEE788, a dual tyrosine kinase inhibitor of EGFR and VEGFR, in combination with paclitaxel would inhibit experimental FTC bone lesions and preserve bone structure. We tested this hypothesis using the human WRO FTC cell line. In culture, AEE788 inhibited the EGF-mediated phosphorylation of EGFR, VEGFR2, mitogen-activated protein kinase and Akt in culture. AEE788, alone and in combination with paclitaxel, inhibited cell growth and induced apoptosis. When WRO cells were injected into the tibia of nude mice, tumor and endothelial cells within the lesions expressed phosphorylated EGFR, VEGFR, Akt and mitogen-activated protein kinase that were inhibited by the oral administration of AEE788. Therapy consisting of orally given AEE788 and i.p. injected paclitaxel induced a high level of apoptosis in tumor-associated endothelial cells and tumor cells with the inhibition of tumor growth in the bone and the preservation of bone structure. Collectively, these data show that blocking the phosphorylation of EGFR and VEGFR with AEE788 combined with paclitaxel can significantly inhibit experimental human FTC in the bone of nude mice

Forearm vasodilator responses to environmental stress and reactive hyperaemia are impaired in young South Asian men

© 2018, The Author(s). Purpose: Prevalence of cardiovascular disease (CVD) is greater in South Asians (SAs) than White Europeans (WEs). Endothelial dysfunction and blunted forearm vasodilatation to environmental stressors have been implicated in CVD. We investigated whether these features are present in young SA men. Methods: In 15 SA and 16 WE men (19–23 years), we compared changes in forearm blood flow, arterial blood pressure (ABP), forearm vascular conductance (FVC), heart rate, and electrodermal resistance (EDR; sweating) following release of arterial occlusion (reactive hyperaemia endothelium-dependent) and 5 single sounds at 5–10 min intervals (stressors). Results: All were normotensive. Peak reactive hyperaemia was smaller in SAs than WEs (FVC increase: 0.36 ± 0.038 vs 0.44 ± 0.038 units; P < 0.05). Furthermore, in WEs, mean FVC increased at 5, 15, and 20 s of each sound (vasodilatation), but increased at 5 s only in SAs, decreasing by 20 s (vasoconstriction). This reflected a smaller proportion of SAs showing forearm vasodilatation at 15 s (5/15 SAs vs 11/16 WEs: P < 0.01), the remainder showing vasoconstriction. Concomitantly, WEs showed greater bradycardia and EDR changes. Intra-class correlation analyses showed that all responses were highly reproducible over five sounds in both WEs and SAs. Moreover, sound-evoked changes in ABP and FVC were negatively correlated in each ethnicity (P < 0.01). However, WEs showed preponderance of forearm vasodilatation and depressor responses; SAs showed preponderance of vasoconstriction and pressor responses. Conclusions: Endothelium-dependent vasodilatation is blunted in young SA men. This could explain their impaired forearm vasodilatation and greater pressor responses to repeated environmental stressors, so predisposing SAs to hypertension and CVD

Fully automated, inline quantification of myocardial blood flow with cardiovascular magnetic resonance: repeatability of measurements in healthy subjects

Background: Non-invasive assessment of myocardial ischaemia is a cornerstone of the diagnosis of coronary artery disease. Measurement of myocardial blood flow (MBF) using positron emission tomography (PET) is the current reference standard for non-invasive quantification of myocardial ischaemia. Dynamic myocardial perfusion cardiovascular magnetic resonance (CMR) offers an alternative to PET and a recently developed method with automated inline perfusion mapping has shown good correlation of MBF values between CMR and PET. This study assessed the repeatability of myocardial perfusion mapping by CMR in healthy subjects. Methods: Forty-two healthy subjects were recruited and underwent adenosine stress and rest perfusion CMR on two visits. Scans were repeated with a minimum interval of 7 days. Intrastudy rest and stress MBF repeatability were assessed with a 15-min interval between acquisitions. Interstudy rest and stress MBF and myocardial perfusion reserve (MPR) were measured for global myocardium and regionally for coronary territories and slices. Results: There was no significant difference in intrastudy repeated global rest MBF (0.65 ± 0.13 ml/g/min vs 0.62 ± 0.12 ml/g/min, p = 0.24, repeatability coefficient (RC) =24%) or stress (2.89 ± 0.56 ml/g/min vs 2.83 ± 0.64 ml/g/min, p = 0.41, RC = 29%) MBF. No significant difference was seen in interstudy repeatability for global rest MBF (0.64 ± 0.13 ml/g/min vs 0.64 ± 0.15 ml/g/min, p = 0.80, RC = 32%), stress MBF (2.71 ± 0.61 ml/g/min vs 2.55 ± 0.57 ml/g/min, p = 0.12, RC = 33%) or MPR (4.24 ± 0.69 vs 3.73 ± 0.76, p = 0.25, RC = 36%). Regional repeatability was good for stress (RC = 30–37%) and rest MBF (RC = 32–36%) but poorer for MPR (RC = 35–43%). Within subject coefficient of variation was 8% for rest and 11% for stress within the same study, and 11% for rest and 12% for stress between studies. Conclusions: Fully automated, inline, myocardial perfusion mapping by CMR shows good repeatability that is similar to the published PET literature. Both rest and stress MBF show better repeatability than MPR, particularly in regional analysis

Regional release and removal of catecholamines and extraneuronal metabolism to metanephrines

Contains fulltext : 21021___.PDF (publisher's version ) (Open Access

Deep learning-based defect detection in industrial CT volumes of castings

International audienceIndustrial X-ray computed tomography (CT) has proven to be one of the most powerful non-destructive testing (NDT) methods for the inspection of light metal castings. The generated CT volume allows for the internal and external geometry of the specimen to be measured, casting defects to be localised and their statistical properties to be investigated. On the other hand, CT volumes are very prone to artefacts that can be mistaken for defects by conventional segmentation algorithms. These artefacts require trained operators to distinguish them from real defects, which makes CT inspection very time consuming if it is to be implemented on the production line. Foundries using this inspection method are constantly looking for a module that can perform this interpretation automatically. Based on CT data of aluminium alloy automotive and aerospace specimens provided by industrial partners, an automated approach for the analysis of discontinuities inside CT volumes is developed in this paper based on a two-stage pipeline: 2D segmentation of CT slices with automatic deep segmentation using U-Net to detect suspicious greyscale discontinuities; and classification of these discontinuities into true alarms (defects) or false alarms (artefacts and noise) using a new convolutional neural network classifier called CT-Casting-Net. The choice of each model and the training results are presented and discussed, as well as the efficiency of the approach as an automatic defect detection algorithm for industrial CT volumes using metrics relevant to the field of non-destructive testing. The approach is tested on six new CT volumes with 301 defects and achieves an object-level recall of 99%, a precision of 87% and a voxel-level intersection-over-union (IoU) of 62%