Yuhei Irie

Assessment of the usefulness of presepsin (soluble CD14 subtype) in septic patients

Sepsis is a life-threatening condition characterized by a whole-body inflammatory state. The early diagnosis and treatments of sepsis will improve the outcome of patients. The aim of this study was to compare blood levels of presepsin (renamed from soluble CD14 subtype), procalcitonin (PCT), IL-6 and C-reactive protein (CRP) and to investigate the most useful biomarker for early diagnosis of sepsis.

Involvement of the cystathionine-γ-lyase/Ca v 3.2 pathway in substance P-induced bladder pain in the mouse, a model for nonulcerative bladder pain syndrome

ABSTRACT Hydrogen sulfide (H2S) formed by cystathionine‐&ggr;‐lyase (CSE) enhances the activity of Cav3.2 T‐type Ca2+ channels, contributing to the bladder pain accompanying hemorrhagic cystitis caused by systemic administration of cyclophosphamide (CPA) in mice. Given clinical and fundamental evidence for the involvement of the substance P/NK1 receptor systems in bladder pain syndrome (BPS)/interstitial cystitis (IC), we created an intravesical substance P‐induced bladder pain model in mice and analyzed the possible involvement of the CSE/Cav3.2 pathway. Bladder pain/cystitis was induced by i.p. CPA or intravesical substance P in female mice. Bladder pain was evaluated by counting nociceptive behavior and by detecting referred hyperalgesia in the lower abdomen and hindpaw. The isolated bladder tissue was weighed to estimate bladder swelling and subjected to histological observation and Western blotting. Intravesical substance P caused profound referred hyperalgesia accompanied by little bladder swelling or edema 6‐24 h after the administration, in contrast to i.p. CPA‐induced nociceptive behavior/referred hyperalgesia with remarkable bladder swelling/edema and urothelial damage. The bladder pain and/or cystitis symptoms caused by substance P or CPA were prevented by the NK1 receptor antagonist. CSE in the bladder was upregulated by substance P or CPA, and the NK1 antagonist prevented the CPA‐induced CSE upregulation. A CSE inhibitor, a T‐type Ca2+ channel blocker and gene silencing of Cav3.2 abolished the intravesical substance P‐induced referred hyperalgesia. The intravesical substance P‐induced pain in mice is useful as a model for nonulcerative BPS, and involves the activation of the NK1 receptor/CSE/H2S/Cav3.2 cascade. HighlightsIntravesical substance P caused bladder pain with little urothelial damage.Substance P upregulated an H2S‐forming enzyme in the bladder.Inhibition of the H2S‐forming enzyme blocked the substance P‐induced bladder pain.Cav3.2 knockdown abolished the substance P‐induced bladder pain.Cav3.2 targeted by H2S thus mediates the substance P‐induced bladder pain.

Adsorption of Nafamostat Mesilate on AN69ST Membranes: A Single‐Center Retrospective and in vitro Study

We examined whether AN69ST (acrylonitrile and methallyl sulfonate copolymer) membranes adsorb nafamostat mesilate. This study retrospectively analyzed 87 continuous hemodiafiltration sessions in vivo. We divided the continuous hemodiafiltration sessions into AN69ST and non‐AN69ST groups using the nafamostat mesilate dose and activated clotting time as indicators of nafamostat mesilate adsorption onto the membrane. Furthermore, we studied the in vitro adsorption of nafamostat mesilate from nafamostat mesilate solutions onto four different hemodialysis membranes. This in vivo study shows that nafamostat mesilate doses were significantly higher, but activated clotting times were shorter (P < 0.001) in the AN69ST group than in the non‐AN69ST group. These results suggest that AN69ST adsorbs nafamostat mesilate. Further, the in vitro experiments show that nafamostat mesilate adsorbs AN69ST on membranes significantly more than the other membranes tested. These in vitro and clinical findings provide evidence that AN69ST may adsorb nafamostat mesilate.