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Mechanically, P7C3-A20 stimulated fibroblast growth factor 21 (FGF21) and FGF1 via activating liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK), which further resulted in a reduced nuclear translocation of CREB regulated transcription coactivator 2 (CRTC2). In AMPKα2 knockout mice, the protection of P7C3-A20 against HFD-induced metabolism abnormities and fat accumulation, as well as the elevation of blood FGF21 and FGF1, were abolished. P7C3-A20 increased the gut microbiota species richness. Moreover, it enhanced the proportions of Akkermansia, Lactobacillus and Prevotellaceae whereas reduced the proportions of Enterobacteriaceae, Escherichia, and Parasutterella. SmoothenedAgonist CONCLUSIONS AND IMPLICATIONS The NAD+ boosting agent P7C3-A20 alleviates NAFLD through stimulating FGF21 and FGF1 in an LKB1/AMPK/CRTC2-dependent manner and shaping gut microbiota. This article is protected by copyright. All rights reserved.OBJECTIVE Current haematology reference intervals (RIs) for koalas were developed in northern Australian koalas, using low numbers and/or individuals of unknown Chlamydia pecorum and koala retrovirus (KoRV) status. This study developed haematological RIs for wild, clinically healthy southern Australian koalas of known C. pecorum and KoRV infection status and investigated the effects of population, age and sex. METHODS Haematological RIs were determined for 138 clinically healthy South Australian koalas (Mount Lofty Ranges [MLR], n = 68; Kangaroo Island, n = 70) examined in April 2016 and February 2017, respectively. C. pecorum and KoRV status were determined by PCR. RESULTS RIs for southern koala haematological parameters were established for all koalas based on the finding that there were limited differences in haematological values in koalas with subclinical C. pecorum or KoRV infections (P > 0.05), except KoRV-infected koalas had a lower haematocrit than noninfected koalas. MLR koalas had significantly lower erythrocyte mass and leucocyte counts than Kangaroo Island koalas. Young koalas had significantly lower haemoglobin, haematocrit and higher mean cellular haemoglobin concentration and lymphocyte counts than adult koalas. MLR male koalas had elevated erythrocyte, leucocyte and neutrophil counts compared with MLR females. CONCLUSION The haematological RIs developed in this study are based on a large number of clinically healthy koalas, where subclinical C. pecorum and KoRV infections had no effect on haematological values and will be a valuable tool during clinical examination and disease investigation by veterinarians and researchers Australia-wide. © 2020 Australian Veterinary Association.BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) is a condition caused by a drug-induced immune response. Previous reports had found that CXCL10, also known as interferon-γ-induced protein-10 (IP-10), may participate in the pathogenesis of cutaneous adverse drug reactions; however, the exact role of IP-10 in DRESS and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) remained unknown. OBJECTIVES This comparative prospective cohort study aimed to ascertain the roles of IP-10/CXCR3 axis in DRESS and SJS/TEN. METHODS Plasma IP-10 levels were analyzed, and univariate analyses were conducted to assess the relationship between IP-10, human herpes virus 6 (HHV-6) reactivation, and the development of long-term sequelae. We also performed immunohistochemistry staining using skin specimens and flow cytometry to determine the expression of CXCR3 in peripheral blood mononuclear cells (PBMCs). RESULTS Significantly higher plasma IP-10 levels were observed in DRESS patients with long-term sequelae (effect size (ES)=0.81) and also in those with HHV-6 reactivation (ES=0.83). By immunohistochemistry, more abundant IP-10+ and CXCR3+ cells were demonstrated in the skin lesions of DRESS patients with HHV-6 reactivation. The percentage of CLA+ CXCR3+ CD4+ cells and CLA+ CXCR3+ CD8+ cells was also higher in the PBMCs of HHV-6 reactivated DRESS patients than in those of SJS/TEN patients. CONCLUSIONS Higher plasma IP-10 levels are associated with the development of long-term sequelae in DRESS. Higher IP-10/CXCR3 expression in skin and more abundant CLA+ CXCR3+ CD4+ cells and CLA+ CXCR3+ CD8+ cells were observed in DRESS patients with HHV-6 reactivation. The IP-10/CXCR3 axis is associated with HHV-6 reactivation and development of long-term sequelae in DRESS. This article is protected by copyright. All rights reserved.Eight G protein-coupled P2Y receptor (P2YR) subtypes respond to extracellular adenine and uracil mono- and dinucleotides. P2YRs belong to the δ group of rhodopsin-like GPCRs and contain two structurally distinct subfamilies P2Y1 , 2 , 4 , 6 , and 11 (principally Gq protein-coupled P2Y1 -like) and P2Y12-14 (principally Gi protein-coupled P2Y12 -like) receptors. Brain P2YRs occur in neurons, glial cells and vasculature. Endothelial P2Y1 , P2Y2 , P2Y4 and P2Y6 Rs induce vasodilation, while smooth muscle P2Y2 , P2Y4 and P2Y6 R activation leads to vasoconstriction. Pancreatic P2Y1 and P2Y6 Rs stimulate while P2Y13 R inhibits insulin secretion. Antagonists of P2Y12 R, and potentially P2Y1 R, are antithrombotic agents, and a P2Y2 /P2Y4 R agonist treats dry eye syndrome in Asia. P2YR agonists are generally pro-inflammatory, and antagonists may eventually treat inflammatory conditions. This article reviews recent developments in P2YR pharmacology (using synthetic agonists and antagonists), structure and biophysical properties (using X-ray crystallography, mutagenesis and modeling), physiological and pathophysiological roles, and present and potentially future therapeutic targeting. This article is protected by copyright. All rights reserved.BACKGROUND The cost-effectiveness of albumin-based fluid support in patients with septic shock is currently unknown. METHODS In a simulation study, we compared standard medical practice and systematic 20% albumin infusion. The study population consisted of patients with septic shock admitted to one of the 28 ICUs belonging to the Cub-Réa regional database between 1 January 2014 and 31 December 2016. Cost estimates were based on French diagnosis-related groups and fixed daily prices. Estimation of mortality reduction relied on ALBIOS trial data documenting a Risk Ratio of 0.87 in a non-preplanned subgroup of patients with septic shock. Life expectancy was estimated with follow up data of 184 patients with septic shock admitted in the year 2000 in the same ICUs. Several sensitivity analyses were performed including a one-way Deterministic Sensitivity Analysis (DSA) and a Probabilistic multivariate Sensitivity Analysis (PSA). RESULTS About 6406 patients were included. In the base-case scenario, the mean live years gained with albumin was 0.