Novel mode for neutrophil protease cathepsin G-mediated signaling: membrane shedding of epidermal growth factor is required for cardiomyocyte anoikis

Neutrophils are thought to orchestrate myocardial remodeling during the early progression to cardiac failure through the release of reactive oxygen species, antimicrobial peptides, and proteases. Although neutrophil activation may be beneficial at early stages of disease, excessive neutrophil infiltration can induce cardiomyocyte death and tissue damage. The neutrophil-derived serine protease cathepsin G (Cat.G) has been shown to induce neonatal rat cardiomyocyte detachment and apoptosis by anoikis. However, the involved signaling mechanisms for Cat.G are not well understood. This study identifies epidermal growth factor receptor (EGFR) transactivation as a mechanism whereby Cat.G induces signaling in cardiomyocytes. Cat.G induced a rapid and transient increase in EGFR tyrosine phosphorylation, and inhibition of EGFR kinase activity, either with AG1478 or by expression of kinase inactive EGFR mutants (EGFR-CD533), markedly attenuated EGFR downstream signaling and myocyte anoikis induced by Cat.G. Consistent with this effect of EGFR, high level expression of wild-type EGFR was sufficient to promote myocyte apoptosis. We also found that matrix metalloproteinase-dependent membrane shedding of heparin-binding EGF was involved in Cat.G signaling and that membrane type 1 matrix metalloproteinase activation may constitute a potential target that entails matrix metalloproteinase activation induced by Cat.G. The paradoxical proapoptotic effect of EGFR appeared to be dependent on protein tyrosine phosphatase SHP2 (Src homology domain 2-containing tyrosine phosphatase 2) activation and focal adhesion kinase downregulation. These results show that Cat.G-induced cardiomyocyte apoptosis involves an increase in EGFR-dependent activation of SHP2 that promotes focal adhesion kinase dephosphorylation and subsequent cardiomyocyte anoikis.     

Effects of enhanced viscosity on canine gastric and intestinal motility

BACKGROUND AND AIM: The aim of this study was to investigate the effect of enhanced viscosity on gastric emptying and gastrointestinal motor and myoelectrical activities in dogs. METHOD: The study was performed in eight healthy female hound dogs chronically implanted with four pairs of gastric and two pairs of intestinal serosal electrodes and a duodenal fistula. Each dog was studied in three sessions and fed with three test meals with different viscosity. Gastric emptying was monitored for 2 h simultaneously with gastric and intestinal myoelectrical recordings. RESULTS: The liquid test meal containing either 0.78% or 1.21% of galactomannan significantly delayed gastric emptying but had no effect on postprandial blood glucose levels in comparison with the meal containing no galactomannan. The liquid test meal containing either 0.78% or 1.21% of galactomannan significantly increased the frequency and strength of intestinal motility but had no effect on intestinal slow wave rhythms. The product with enhanced viscosity had no effect on gastric motor activity or gastric slow waves. CONCLUSION: It was concluded that enhanced viscosity delays gastric emptying, increases postprandial intestinal but not gastric motility, and has no effects on gastric or intestinal slow waves.     

Unusual presentations of eosinophilic gastroenteritis： Case series and review of literature

Eosinophilic gastroenteritis （EG） is an uncommon disease characterized by focal or diffuse eosinophilic infiltration of the gastrointestinal tract, and is usually associated with dyspepsia, diarrhea and peripheral eosinophilia.Diffuse gastrointestinal tract and colonic involvement are uncommon. The endoscopic appearance may vary from normal to mucosal nodularity and ulceration.Gastrointestinal obstruction is unusual and is associated with predominantly muscular disease. We present five unusual cases of EG associated with gastric outlet and duodenal obstruction. Two cases presented with acute pancreatitis and one had a history of pancreatitis.Four cases responded well to medical therapy and onehad recurrent gastric outlet obstruction that required surgery. Four out of the five cases had endoscopic and histological evidence of esophagitis and two had colitis.Two patients had ascites. These cases reaffirm that EG is a disorder with protean manifestations and may involve the entire gastrointestinal tract. Gastric outletand/or small bowel obstruction is an important though uncommon presentation of EG. It may also presentas esophagitis, gastritis with polypoid lesions, ulcers or erosions, colitis and pancreatitis and may mimic malignancy.     

Incidental finding of arteria lusoria during transradial coronary catheterization: Significance in interventional cardiology

Arteria lusoria is the most common anomaly of the aortic arch with an incidence of 0.5%–2.5%. It is mostly diagnosed incidentally while performing imaging for evaluation of other unrelated medical conditions. The aberrant right subclavian artery arises beyond the origin of the left subclavian artery from the aortic arch. This results in a complex right‐subclavian‐aortic anatomy which leads to difficulty in transradial coronary angiography. This can lead to prolonged procedure time and increased use of catheters by unaware interventionists. This is even more important if this is encountered in the setting of an acute myocardial infarction. Our review takes into account clinical significance of this uncommon anomaly in the field of interventional cardiology.     

Thrombelastographic hypercoagulability and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial): a randomized controlled trial

A hypercoagulable state has, in observational studies, been associated with increased risk of thromboembolic events. The aim of this trial was to study whether dual antiplatelet therapy (DAPT) with clopidogrel in addition to aspirin could reduce the rate of graft occlusions, thromboembolic events, and death compared to aspirin monotherapy in hypercoagulable patients undergoing coronary artery bypass surgery. A total of 1683 patients were screened for eligibility, among which 165 patients were randomized and 133 patients underwent multislice computed tomography scan to evaluate their grafts. Thrombelastography (TEG) and multiplate aggregometry were performed before and after surgery, and again at three months follow up. TEG hypercoagulability was defined as the maximum amplitude above 69 mm. At three months follow up, 17 out of 66 (25.7%) DAPT patients and 15 of 67 (22.4%) aspirin patients had significant graft stenosis or occlusions (p = 0.839). Saphenous vein grafts (SVGs) were stenosed or occluded in 15 (22.7%) patients in the DAPT group and 7 (10.4%) in the aspirin group (p = 0.167). Thromboembolic events and death after the second postoperative day (when clopidogrel was started) were numerically, but not statistically, lower in the DAPT group, 3 (3.8%) vs. 8 (9.9%), p = 0.211. In univariate logistic regression analysis, only postoperative day 4 platelet response to aspirin measured with multiplate was correlated with graft occlusion, OR 1.020 [1.002–1.039], p = 0.033. This is the first trial to test the hypothesis of intensified antiplatelet therapy in hypercoagulable patients. Due to the low enrollment and high loss to follow up, our results can only be viewed as hypothesis generating. We found a high rate of graft occlusions in this patient population. Our results were not suggestive of that DAPT improved saphenous vein graft patency. A trend was observed in patients on DAPT toward fewer MI and deaths. Postoperative response to aspirin therapy was found to be associated with early SVG occlusion.     

HPV Genotyping 9G Membrane Test

The results of the genital human papillomavirus (HPV) detection in 439 cervical samples by cervical cytology were compared with sequencing analysis and a newly developed HPV genotyping 9G membrane test. The excellent sensitivity and specificity of the HPV genotyping 9G membrane test was assured by a signal to noise ratio of more than 300 and a target hybridization to non-target hybridization ratio of 300 ~ 400 at 25 °C. The final results can be obtained in 29 min by simple loading of the hybridization and washing solutions and scanning the membranes without any drying steps or special handling. The 100% identical results of the HPV genotyping 9G membrane test with sequencing results in 439 clinical samples demonstrate significant clinical application for this test. HPV genotyping 9G membrane tests can identify and discriminate five HR-HPV genotypes which are prevalent in almost 87% of cervical cancer cases. Its simple handling makes the HPV genotyping 9G membrane test a very convenient platform for accurate HPV genotyping.     

Using transcutaneous carbon dioxide monitor (TOSCA 500) to detect respiratory failure in patients with amyotrophic lateral sclerosis: A validation study

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition, respiratory failure being the commonest cause of death. Quality of life and survival can be improved by supporting respiratory function with non-invasive ventilation. Transcutaneous carbon dioxide monitoring is a non-invasive method of measuring arterial carbon dioxide levels enabling simple and efficient screening for respiratory failure. The aim of this study was to validate the accuracy of carbon dioxide level recorded transcutaneously with a TOSCA 500 monitor. It is a prospective, observational study of 40 consecutive patients with ALS, recruited from a specialist ALS clinic. The partial pressure of carbon dioxide (PCO(2)) in each patient was determined by both transcutaneous monitoring and by an arterialized ear lobe capillary blood sample. The carbon dioxide (CO(2)) levels obtained with these two methods were compared by Bland-Altman analysis. The results showed that the mean difference between arterialized and transcutaneous readings was - 0.083 kPa (SD 0.318). The Bland-Altman limits of agreement ranged from 0.553 to - 0.719 kPa. The difference was ?0.5 kPa, with a maximum recorded difference of 0.95 kPa. In conclusion, non-invasive carbon dioxide monitoring using a TOSCA monitor is a useful clinical tool in neurology practice. Users should be aware of the possibility of occasional inaccurate readings. A clinically unexpected or incompatible reading should be verified with a blood gas analysis, especially when a decision to provide ventilatory support is required.     

An inclusive review and perspective on Cu-based materials for electrochemical water splitting

In recent years, there has been a resurgence of interest in developing green and renewable alternate energy sources as a solution to the energy and environmental problems produced by conventional fossil fuel use. As a very effective energy transporter, hydrogen (H₂) is a possible candidate for the future energy supply. Hydrogen production by water splitting is a promising new energy option. Strong, efficient, and abundant catalysts are required for increasing the efficiency of the water splitting process. Cu-based materials as an electrocatalyst have shown promising results for application in the Hydrogen Evolution Reaction (HER) and Oxygen Evolution Reaction (OER) in water splitting. In this review, our aim is to cover the latest developments in the synthesis, characterisation, and electrochemical behaviour of Cu-based materials as a HER, and OER electrocatalyst, highlighting the impact that these advances have had on the field. It is intended that this review article will serve as a roadmap for developing novel, cost-effective electrocatalysts for electrochemical water splitting based on nanostructured materials with particular emphasis on Cu-based materials for electrocatalytic water splitting.

In recent years, there has been a resurgence of interest in developing green and renewable alternate energy sources as a solution to the energy and environmental problems produced by conventional fossil fuel use.