Sivelestat relaxes vascular smooth muscle contraction in human gastric arteries

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Sivelestat sodium hydrate (sivelestat) is a novel synthetic drug and specific inhibitor of neutrophil elastase that has been approved in Japan as a treatment for acute lung injury associated with systemic inflammatory response syndrome. It is important to determine how sivelestat affects hemodynamics and the regulatory mechanisms of vascular smooth muscle (VSM). We recently found that sivelestat relaxes porcine coronary artery VSM via selective inhibition of Ca2+ sensitization induced by a receptor agonist without affecting the normal Ca2+-induced contraction. Although sivelestat relaxes porcine artery, its effects on human artery are unknown; therefore, the purpose of the present study was to assess the effects of sivelestat on human artery. In the present study, sivelestat induced concentration-dependent (1 × 10−6 to 3 × 10−4 M) vasorelaxation in U46619 (1 nM) and sphingosylphosphorylcholine (SPC) (30 mM)-precontracted human gastric artery with or without endothelium, but sivelestat did not induce vasorelaxation in conditions of high K+ (40 mM) depolarization. Sivelestat inhibited VSM contraction by an agonist and SPC, and it did not affect Ca2+-induced normal physiologic contraction (AU)

Sivelestat relaxes vascular smooth muscle contraction in human gastric arteries.

Sivelestat sodium hydrate (sivelestat) is a novel synthetic drug and specific inhibitor of neutrophil elastase that has been approved in Japan as a treatment for acute lung injury associated with systemic inflammatory response syndrome. It is important to determine how sivelestat affects hemodynamics and the regulatory mechanisms of vascular smooth muscle (VSM). We recently found that sivelestat relaxes porcine coronary artery VSM via selective inhibition of Ca(2+) sensitization induced by a receptor agonist without affecting the normal Ca(2+)-induced contraction. Although sivelestat relaxes porcine artery, its effects on human artery are unknown; therefore, the purpose of the present study was to assess the effects of sivelestat on human artery. In the present study, sivelestat induced concentration-dependent (1 × 10(-6) to 3 × 10(-4) M) vasorelaxation in U46619 (1 nM) and sphingosylphosphorylcholine (SPC) (30 mM)-precontracted human gastric artery with or without endothelium, but sivelestat did not induce vasorelaxation in conditions of high K(+) (40 mM) depolarization. Sivelestat inhibited VSM contraction by an agonist and SPC, and it did not affect Ca(2+)-induced normal physiologic contraction.

Survival case of Vibrio vulnificus infection with multiple endocrine neoplasia type I.

A 35-year-old female with malabsorption syndrome who underwent a pancreatoduodenectomy for multiple endocrine adenomatosis 13 years prior was admitted to our hospital with diarrhea, general fatigue, high fever, and eruption in the lower legs. The patient had consumed raw shrimp a few days before onset and presented systemic inflammatory response syndrome at the time of hospitalization. Vibrio vulnificus was isolated from a blood culture performed before admission to the intensive care unit. We excised necrotizing tissue in the legs after improvement of her general condition. During the treatment process, glucose, catecholamine, and appropriate antibiotics were administered for hypoglycemia, hypotension, and high fever, respectively. The patient was discharged 107 days after contracting the disease. Of 18 septic patients with V. vulnificus infection admitted to our hospital, this was the first to develop septicemia in the absence of a previous liver dysfunction. In order to prevent this type of fatal infection, public education for immuno-compromised individuals as well as those with liver disease is essential. For early diagnosis and appropriate treatment, more effective strategies are required, such as the establishment of a network system where family physicians and emergency hospital staff could discuss information regarding high-risk patients.