Relation between myocardial response to dobutamine stress and sympathetic nerve activation in patients with idiopathic dilated cardiomyopathy: A comparison of123I-MIBG scintigraphic and echocardiographic data

It is likely that a close association exists between findings obtained by two methods: dobutamine stress echocardiography and 123I-MIBG scintigraphy. Both of these methods are associated with beta-adrenergic receptor mechanisms. This study was conducted to demonstrate the relation between myocardial response to dobutamine stress and sympathetic nerve release of norepinephrine in the failing heart. In 12 patients with heart failure due to idiopathic dilated cardiomyopathy, the myocardial effects of dobutamine stress were evaluated by low-dose dobutamine stress echocardiography: and sympathetic nerve function was evaluated by scintigraphic imaging with iodine-123 [123I] meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine. Echocardiography provided quantitative assessment of wall motion and left ventricular dilation; radiotracer studies with 123I-MIBG provided quantitative assessment of the heart-to-mediastinum (H/M) uptake ratio and washout rate. Results showed that H/M correlated with baseline wall motion (r = 0.682, p = 0.0146), wall motion after dobutamine stress (r = 0.758, p = 0.0043), the change in wall motion (r = 0.667, p = 0.0178), and with left ventricular diastolic diameter (r = 0.837, p = 0.0007). In addition, the 123I-MIBG washout rate correlated with baseline wall motion (r = 0.608, p = 0.0360), wall motion after dobutamine stress (r = 0.703, p = 0.0107), and with the change in wall motion (r = 0.664, p = 0.0185). Wall motion, especially in the myocardial response to dobutamine stress, is related to sympathetic nerve activity in heart failure.     

Fatigue-induced changes in longitudinal relaxation time determined by magnetic resonance imaging

Longitudinal relaxation time (T₁) determined by 3.0-T magnetic resonance imaging of the tibialis anterior and extensor digitorum longus muscles increased gradually with muscle fatigue caused by three 120-s periods of repeated ankle dorsiflexion separated by 5-min rest periods. T₁ values decreased in the recovery period, although they remained higher than the preexercise values. T₁ values for the soleus muscle were unchanged throughout the experiment. Results suggest that muscle T₁ values increase with increasing muscle fatigue.     

Negative regulation of cell motile and invasive activities by lysophosphatidic acid receptor-3 in colon cancer HCT116 cells

Lysophosphatidic acid (LPA) mediates a wide range of biological responses with G protein-coupled transmembrane receptors (LPA receptors). So far, at least six types of LPA receptors (LPA receptor-1 (LPA₁) to LPA₆) have been identified. Recently, it has been reported that LPA₃ indicates opposite effects on cellular functions of cancer cells. In the present study, to assess a biological role of LPA₃ on cell migration ability of colon cancer cells, we generated LPA receptor-3 (LPAR3) knockdown (HCT-sh3-3) cells from HCT116 and measured cell motile and invasion activities. In motility assay with a cell culture insert, HCT-sh3-3 cells showed significantly high cell motile activity, compared with control cells. For invasion assay, the filter was coated with Matrigel. The invasive activity of HCT-sh3-3 cells was significantly higher than that of control cells. Furthermore, we also examined the effects of LPAR3 knockdown on the interaction between colon cancer cells and endothelial F-2 cells. When F-2 cells were cultured with serum-free DMEM containing a supernatant from HCT-sh3-3 cells, the cell growth rate and migration activity of F-2 cells were significantly stimulated, associating with the elevated expressions of vascular endothelial growth factor (VEGF)-A and VEGF-C genes in HCT-sh3-3 cells. These results suggest that LPA₃ may act as a negative regulator on cell motile and invasive abilities of colon cancer HCT116 cells.     

Diagnostic accuracy,yield, and comparative effectiveness of whole-body computed tomography in blunt trauma: A protocol for systematic review and meta-analysis

Objectives:Controversies emerge over routine performances of whole-body computed tomography (WBCT) in patients with blunt polytrauma. The existing randomized and non-randomized evidence is inconclusive, and during observations of non-trauma, incidental findings, detected by WBCT, have left uncertainty regarding their consequences and optimal management. Additionally, previous meta-analyses have failed to address the limitations of primary studies and issues associated with incidental findings. Therefore, we planned a new systematic review to address these points.Methods:We will search the PubMed, EMBASE, and Cochrane Central databases from inception to December 31, 2020, with no language restriction and perform full-text evaluation of potentially relevant articles. We will include prospective and retrospective studies with a single-gate design that assessed diagnostic accuracy and/or yield of WBCT to detect traumatic injuries, and studies that assessed incidental findings detected by WBCT. Additionally, we will include randomized controlled trials and non-randomized comparative studies that assessed the effectiveness of WBCT against conventional care, including selective computed tomography (CT). Studies of patients of all ages with blunt traumatic injuries, assessed at an emergency department, will be included. Two reviewers will extract data and rate the study validity via standard quality assessment tools. The primary outcome of interest will be reduction in mortality. Our secondary outcomes will include diagnostic accuracy and yield, detection of incidental findings and clinical outcomes associated with these detections, and improvement in other non-mortality clinical outcomes. We will qualitatively assess study, patient, and intervention characteristics and clinical outcomes. If appropriate, we will perform random-effects model meta-analyses to obtain summary estimates. Finally, we will assess the certainty of evidence by the grading the quality of evidence and strength of recommendations.Ethics and dissemination:Ethics approval is not applicable, as this is a secondary analysis of publicly available data. The review results will be submitted for publication in peer-reviewed journals.Prospero registration:CRD42020187852.     

The renin-angiotensin system is involved in the production of plasminogen activator inhibitor type 1 by cultured endothelial cells in response to chylomicron remnants.

Triglyceride-rich lipoproteins have been suggested to promote atherosclerosis. Plasminogen activator inhibitor type 1 (PAI-1) plays an important role in the events of cardiovascular pathophysiology. The renin-angiotensin system influences various vascular functions, including PAI-1 production. We examined whether or not chylomicron remnants increased PAI-1 mRNA and protein production in endothelial cells and whether or not an inhibition of the renin-angiotensin system interfered with this effect. Chylomicron remnants were isolated from functionally hepatectomized rats injected with chylomicrons. Human umbilical vein endothelial cell cultures (HUVECs) were incubated with chylomicron remnants with or without an angiotensin-converting enzyme inhibitor (temocaprilat), an angiotensin II receptor type 1 antagonist (RNH-6270), or an angiotensin II receptor type 2 antagonist (PD123319). Chylomicron remnants increased PAI-1 secretion in HUVECs (0.5 microg/ml; 128.3 +/- 6.1%, the mean +/- SEM) as well as angiotensin II (10 nmol/l; 130.7 +/- 9.5%) in 18 h, as compared with the controls, as well as stimulated PAI-1 mRNA expression to a maximum level at 4 h. Temocaprilat and RNH-6270, but not PD123319, attenuated all of these effects. Chylomicron remnants enhanced nuclear extract binding to a very low-density lipoprotein response element in the PAI-1 promoter region and activated nuclear factor-kappaB. Extracellular signal-regulated kinase (ERK 1/2) was phosphorylated in response to chylomicron remnants. These effects were inhibited by temocaprilat or RNH-6270. In conclusion, chylomicron remnants increased protein secretion and mRNA expression of PAI-1 in HUVECs. Inhibition of the renin-angiotensin system reduced this stimulation.     

Comparison of the circulatory effects of continuous renal replacement therapy using AN69ST and polysulfone membranes in septic shock patients: A retrospective observational study

The acrylonitrile‐co‐methallyl sulfonate surface‐treated (AN69ST) membrane is expected to improve hemodynamics in patients with sepsis through cytokine adsorption. However, the clinical literature on AN69ST membranes is very limited. We aimed to compare the circulatory effects of continuous renal replacement therapy (CRRT) between patients using the AN69ST membrane and polysulfone (PS) membrane (a nonadsorbing membrane). This retrospective observational study enrolled 38 patients with septic shock, as defined by Sepsis‐3 criteria, who required CRRT from April 2013 to March 2018. Those who died within 24 hours after CRRT initiation and received polymyxin B‐immobilized fiber column direct hemoperfusion, extracorporeal membrane oxygenation, and CRRT using other membranes were excluded. The primary outcome was the vasopressor dependency index during the 12 hours after CRRT initiation, which was calculated as (inotropic score)/(mean arterial pressure). Of 38 patients analyzed, 16 underwent CRRT with an AN69ST membrane and 22 with a PS membrane. The median patient age was 68 years, and the median Acute Physiology and Chronic Health Evaluation (APACHE) II score at intensive care unit admission was 29.5. The vasopressor dependency index decreased significantly during the 12 hours after CRRT initiation in both groups (AN69ST: from 0.50 ± 0.43 to 0.33 ± 0.27 [P < .05], PS: from 0.34 ± 0.30 to 0.21 ± 0.22 [P < .05]). The time course of the vasopressor dependency index during the 12 hours did not differ between the two groups (P = .11). The vasopressor dependency index decreased significantly after CRRT initiation in both groups. The time course of the vasopressor dependency index did not differ between the groups.