Background: Linagliptin, the only bile-excreted dipeptidyl peptidase-4 (DPP-4) inhibitor, is a therapeutic drug for patients with diabetes receiving hemodialysis, for whom inflammation is a prognosis-related factor, because of its potential anti-inflammatory effects. Although the anti-inflammatory effects of linagliptin in vivo are reported, no study has described these effects in vitro. DPP-4 degrades glucagon-like peptide-1 (GLP-1), which is known to have anti-inflammatory properties. Since GLP-1 is a gut hormone secreted by intestinal L cells, in vivo examination of the GLP-1-independent anti-inflammatory effects of DPP-4 inhibitors is difficult. We evaluated the mitogen-activated protein kinase (MAPK)-dependent, GLP-1-independent, anti-inflammatory effects of linagliptin in lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) which do not secrete GLP-1. Furthermore, to determine whether linagliptin has unique pharmacological actions compared with other DPP-4 inhibitors, we assessed the anti-inflammatory effects of sitagliptin (a DPP-4 inhibitor without xanthine-related skeletal system activity), caffeine (a phosphodiesterase inhibitor), loxoprofen, and diclofenac sodium. Methods: HUVECs were cultured for 24 h at densities of 1-2 × 10 5 cells/mL. We pretreated HUVECs with or without linagliptin (1, 5, 10, 50, and 100 nM), 150 nM sitagliptin, 50 nM caffeine, 17 μM loxoprofen, or 1.3 μM diclofenac sodium for 1 h prior to incubation with LPS. The concentration of LPS used (1 μg/mL) was sufficient to induce an inflammatory response in HUVECs. Five hours after incubation with LPS, culture media was evaluated for interleukin (IL)-6 expression. Intranuclear p65 (a subunit of nuclear factor kappa-B (NFκB)) levels were measured 5 h after treatment with LPS and 50 nM linagliptin, while phosphorylated p38 MAPK levels were measured in the cytosolic fractions obtained 30 min after treatment with LPS and 50 nM linagliptin.

Among patients on haemodialysis with both anaemia and hyperphosphatemia, hepcidin-25/erythroferrone ratio could be a novel prognostic marker for increases in Hb levels following ferric citrate hydrate administration. ABSTRACT:Background/Aims: Hepcidin-25 (HEP-25) and erythroferrone (ERFE) are key

Recently, postmortem imaging is sometimes used as an alternative to conventional autopsy. However, there are few case reports of postmortem imaging of dialysis patients. Here, we report a fatal case of gas gangrene involving a 76-year-old man who underwent dialysis. He died suddenly before a diagnosis could be established. Immediately after his death, postmortem computed tomography (PMCT) revealed gas accumulation in his right upper extremity and ascending aorta. Gas gangrene progresses rapidly and may sometimes result in sudden death before it is diagnosed. In this case, PMCT findings were useful to diagnose gas gangrene. Intravascular gas is a common finding on PMCT and is generally caused by cardiopulmonary resuscitation and decomposition. However, the detection of gas in the ascending aorta by PMCT was not described previously. Moreover, Gram stain and culture of the exudate showed anaerobic Gram-positive bacilli which suggested that the gas generation in the blood was caused by Clostridia species. To the best our knowledge, this is the first report of a dialysis patient whose cause of death was determined as gas gangrene using PMCT.

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