Nonalcoholic fatty liver disease (NAFLD) associates with obesity and type 2 diabetes. Hypoactive AMP-activated protein kinase (AMPK), hyperactive mammalian target of rapamycin (mTOR) signaling, and macrophage-mediated inflammation are mechanistically linked to NAFLD. Studies investigating roles of arginase particularly the extrahepatic isoform arginase-II (Arg-II) in obesity-associated NAFLD showed contradictory results. Here we demonstrate that Arg-II−/− mice reveal decreased hepatic steatosis, macrophage infiltration, TNF-α and IL-6 as compared to the wild type (WT) littermates fed high fat diet (HFD). A higher AMPK activation (no difference in mTOR signaling), lower levels of lipogenic transcription factor SREBP-1c and activity/expression of lipogenic enzymes were observed in the Arg-II−/− mice liver. Moreover, release of TNF-α and IL-6 from bone marrow-derived macrophages (BMM) of Arg-II−/− mice is decreased as compared to WT-BMM. Conditioned medium from Arg-II−/−-BMM exhibits weaker activity to facilitate triglyceride synthesis paralleled with lower expression of SREBP-1c and SCD-1 and higher AMPK activation in hepatocytes as compared to that from WT-BMM. These effects of BMM conditioned medium can be neutralized by neutralizing antibodies against TNF-α and IL-6. Thus, Arg-II-expressing macrophages facilitate diet-induced NAFLD through TNF-α and IL-6 in obesity.

Coronary artery ligations to induce myocardial infarction (MI) in mice and rats are widely used in preclinical investigation. However, myocardial ischemic damage and subsequent infarct size are highly variable. The lack of standardization of the model impairs the probability of effective translation to the clinic. Cardiac Troponin I (cTnI) is a major clinically relevant biomarker.Aim: In the present study, we investigated the prognostic value of cTnI for early estimation of the infarct size.Methods and Results: Infarcts of different sizes were induced in mice and rats by ligation, at a random site, of the coronary artery. Kinetics of the plasma levels of cTnI were measured. Heart function was evaluated by echocardiography, the percentage of infarcted left ventricle and infarct expansion index were assessed from histological section. We observed that plasma cTnI level peaked at 24 h in the infarcted rats and between 24 and 48 h in mice. Sham operated animals had a level of cTnI below 15 ng/mL. Infarct expansion index (EI) assessed 4 weeks after ligation showed a large variation coefficient of 63 and 71% in rats and mice respectively. We showed a significative correlation between cTnI level and the EI demonstrating its predictive value for myocardial injury in small animal models.Conclusion: we demonstrated the importance of cTnI plasma level as a major early marker to assist in the optimal and efficient management of MI in laboratory animals model. The presented results stress the need for comparable biomarkers in the animal model and clinical trials for improved translation.

Background Hemolytic blood samples are the number one cause for specimen rejection at emergency departments. Triggered by unsuitable blood sampling material or incorrect handling and a related strong vacuum force, hemolytic samples often must be retaken. The objective of this study was to assess whether correct manual aspiration using S-Monovette® could reduce the number of hemolytic samples. Methods Between January and April 2019, a head-to-head study was conducted. Whereas in the first eight weeks, all specimens were collected using Vacutainer®, in the second eight weeks, blood was taken using S-Monovette® in aspiration mode. Specimens were categorized into five classes (0–30, 31–50, 51–75, 76–100, and 101+ mg/dl of cell-free hemoglobin) and for the statistical analyses, all samples exceeding 30 mg/dl were classified as hemolytic. Results Data were collected on 4794 blood specimens (Vacutainer®: 2634 samples, S-Monovette®: 2160 samples). While the percentage of non-hemolytic samples (HI of 0–30 mg/dl) was substantially higher for specimens drawn by S-Monovette® (95.7 %) than Vacutainer® (83.0 %), the opposite was true for all HI categories above 30 mg/dl. Importantly, the reduction of hemolytic samples took place immediately following the imposition of S-Monovette® and remained stable at a low level until the end of the study. Conclusions Based on our results, we conclude that switching to S-Monovette® in manual aspiration mode in the blood sampling process could be highly beneficial, not only from a financial point of view, but also with regards to reducing unnecessary tasks and stress for nursing staff and improving patient outcome overall.