The TNF-derived TIP peptide activates the epithelial sodium channel and ameliorates experimental nephrotoxic serum nephritis.

In mice, the initial stage of nephrotoxic serum-induced nephritis (NTN) mimics antibody-mediated human glomerulonephritis. Local immune deposits generate tumor necrosis factor (TNF), which activates pro-inflammatory pathways in glomerular endothelial cells (GECs) and podocytes. Because TNF receptors mediate antibacterial defense, existing anti-TNF therapies can promote infection; however, we have previously demonstrated that different functional domains of TNF may have opposing effects. The TIP peptide mimics the lectin-like domain of TNF, and has been shown to blunt inflammation in acute lung injury without impairing TNF receptor-mediated antibacterial activity. We evaluated the impact of TIP peptide in NTN. Intraperitoneal administration of TIP peptide reduced inflammation, proteinuria, and blood urea nitrogen. The protective effect was blocked by the cyclooxygenase inhibitor indomethacin, indicating involvement of prostaglandins. Targeted glomerular delivery of TIP peptide improved pathology in moderate NTN and reduced mortality in severe NTN, indicating a local protective effect. We show that TIP peptide activates the epithelial sodium channel(ENaC), which is expressed by GEC, upon binding to the channel's α subunit. In vitro, TNF treatment of GEC activated pro-inflammatory pathways and decreased the generation of prostaglandin E2 and nitric oxide, which promote recovery from NTN. TIP peptide counteracted these effects. Despite the capacity of TIP peptide to activate ENaC, it did not increase mean arterial blood pressure in mice. In the later autologous phase of NTN, TIP peptide blunted the infiltration of Th17 cells. By countering the deleterious effects of TNF through direct actions in GEC, TIP peptide could provide a novel strategy to treat glomerular inflammation.

Alcohol and drug screening and brief intervention behaviors among advanced practice registered nurse (APRN) students in clinical settings.

Previous research on training health professionals to identify and address unhealthy alcohol and drug use in patients through screening, brief intervention, and referral to treatment (SBIRT) has found that training increases knowledge about substance use and increases students' confidence in addressing substance use in patients. To date, however, there is little information on how health professional students integrate SBIRT into individual practice. Within a U.S. SBIRT training consortium, advanced practice registered nurse (APRN) students were required to practice SBIRT in clinical settings and complete assessment logs for each patient screened. Logs documented results from single item alcohol & drug screening questions; AUDIT or DAST responses; brief intervention (BI)/referral to treatment (RT) steps completed and patients' responses. 113 APRN students completed logs on 538 patients (mean age 44; SD 15.0; 53.5% female). Positive single question alcohol screens were more frequent than positive single question drug screens (55.3% vs. 25.5%). More than one third (36%) of the logs included high-risk AUDIT/DAST scores. The most utilized BI components were discussions regarding consequences of use (76%) and safe levels of use (70%), while the most utilized RT steps included referral to a mutual help group (15%) or a specialty treatment program (8%). Positive screening rates found by APRN students were higher than reported rates in most clinical settings. The logs also demonstrated that APRN students employed many of the SBIRT skills they were taught while also helping identify underutilized SBIRT steps, which may be addressed specifically in future SBIRT trainings.