Effects of dopexamine on the intestinal microvascular blood flow and leucocyte activation in a sepsis model in rats

INTRODUCTION: Dopexamine may be a therapeutic option to improve hepatosplanchnic perfusion in sepsis. To investigate this possibility, we administered dopexamine in an experimental sepsis model in rats. METHODS: This prospective, randomized, controlled laboratory study was conducted in 42 Wistar rats. The animals were divided into three groups. Group 1 served as the control group (CON group). The animals in both groups 2 (LPS group) and 3 (DPX group) received an endotoxin (lipopolysaccharide from Escherichia coli – LPS) infusion (20 mg/kg for 15 minutes). DPX group additionally received dopexamine (0.5 μg/kg per minute over four hours). One half of the animals in each group underwent studies of intestinal microvascular blood flow (IMBF) using laser Doppler fluxmetry. In the other half an intravital microscopic evaluation of leucocyte-endothelial cell interaction in intestinal microcirculation was conducted. Functional capillary density (FCD) in the intestinal mucosa and in the circular as well as longitudinal muscle layer was estimated. RESULTS: One hour after endotoxin challenge, IMBF decreased significantly in LPS group to 51% compared with baseline (P < 0.05). In DPX group (endotoxin plus dopexamine) we found IMBF values significantly higher than those in LPS group (approximately at the level of controls). The impaired FCD following endotoxin challenge was improved by dopexamine in the longitudinal muscle layer (+33% in DPX group versus LPS group; P < 0.05) and in the circular muscle layer (+48% in DPX group versus LPS group; P < 0.05). In DPX group, dopexamine administration reduced the number of firmly adherent leucocytes (-31% versus LPS group; P < 0.05). Plasma levels of tumour necrosis factor-α were reduced by dopexamine infusion (LPS group: 3637 ± 553 pg/ml; DPX group: 1933 ± 201 pg/ml) one hour after endotoxin challenge. CONCLUSION: Dopexamine administration improved IMBF and FCD (markers of intestinal microcirculation) and reduced leucocyte activation (a marker of inflammation) in experimental sepsis

Disciples Discipling Disciples: Implementing Examples of Jesus’s Leadership Lessons

Jesus provides many leadership and discipleship lessons that are applicable to today’s accounting and business students and business leaders. In this paper, we offer instructional resources to better disciple students in the classroom and better prepare them to disciple others they will encounter and lead. We provide four reflection learning assignments that have students consider how they can build their discipleship charac- teristics by studying Jesus’s teachings in the Sermon on the Mount, his examples, and the examples of Christian business leaders who have discipled others. The resources are intended to help instructors and students disciple disciples as disciples of Christ

Radioablation by Image-Guided (HDR) Brachytherapy and Transarterial Chemoembolization in Hepatocellular Carcinoma: A Randomized Phase II Trial

Background and AimsThe aim of this single-center, open-label phase II study was to assess the efficacy of image-guided high-dose-rate (HDR) brachytherapy (iBT) compared with conventional transarterial embolization (cTACE) in unresectable hepatocellular carcinoma.MethodsSeventy-seven patients were treated after randomization to iBT or cTACE, as single or repeated interventions. Crossover was allowed if clinically indicated. The primary endpoint was time to untreatable progression (TTUP). Eligibility criteria included a Child-Pugh score of8 points, absence of portal vein thrombosis (PVT) at the affected liver lobe, and4 lesions. Survival was analyzed by using the Cox proportional hazard model with stratification for Barcelona Clinic Liver Cancer (BCLC) stages.ResultsTwenty patients were classified as BCLC-A (iBT/cTACE 8/12), 35 as BCLC-B (16/19), and 22 as BCLC-C (13/9). The 1-, 2-, and 3-year TTUP probabilities for iBT compared with cTACE were 67.5% versus 55.2%, 56.0% versus 27.4%, and 29.5% versus 11.0%, respectively, with an adjusted hazard ratio (HR) of 0.49 (95% confidence interval 0.27-0.89; p=0.019). The 1-, 2-, and 3-year TTPs for iBT versus cTACE were 56.0% versus 28.2%, 23.9% versus 6.3%, and 15.9% versus 6.3%, respectively, with an adjusted HR of 0.49 (0.29-0.85; p=0.011). The 1-, 2-, and 3-year OS rates were 78.4% versus 67.7%, 62.0% versus 47.3%, and 36.7% versus 27.0%, respectively, with an adjusted HR of 0.62 (0.33-1.16; p=0.136).ConclusionsThis explorative phase II trial showed a superior outcome of iBT compared with cTACE in hepatocellular carcinoma and supports proceeding to a phase III trial