Naoaki Harada

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Antithrombin (AT) prevents Escherichia coli-induced hypotension in animal models of sepsis, and it further reduces the mortality of patients with septic shock. In the present study, we examined whether AT may prevent the endotoxin (ET)-induced hypotension by promoting the endothelial release of prostacyclin (PGI(2)) in rats. Intravenous administration of AT(More)
Insulin-like growth factor-I (IGF-I) exerts beneficial effects on cognitive function. The selective acetylcholinesterase inhibitor donepezil increases serum IGF-I levels in elderly subjects. Because stimulation of sensory neurons induces IGF-I production by releasing calcitonin gene-related peptide (CGRP) in the mouse brain, we hypothesized that donepezil(More)
Metformin, an antidiabetic agent, has been shown to reduce atherothrombotic disease in diabetic patients independent of antihyperglycemic effect. Recent studies have demonstrated that metformin attenuates the proinflammatory responses in human vascular wall cells and macrophages. However, the detailed molecular mechanisms underlying these therapeutic(More)
We investigated the role of prostacyclin (PGI(2)) in the development of compression trauma-induced spinal cord injury (SCI) in rats. When measured after induction of SCI, tissue levels of 6-keto-PGF(1), a stable PGI(2) metabolite, thromboxane B(2) (TXB(2)), a stable metabolite of thromboxane A(2), myeloperoxidase (MPO) activity, and tumor necrosis factor(More)
Antithrombin (AT) supplementation in patients with severe sepsis has been shown to improve organ failures in which activated leukocytes are critically involved. However, the precise mechanism(s) for the therapeutic effects of AT is not well understood. We examined in rats whether AT reduces ischemia/reperfusion (I/R)-induced renal injury by inhibiting(More)
OBJECTIVE To examine whether dalteparin, a low molecular weight heparin, prevents hepatic damage by inhibiting leukocyte activation, we analyzed its effect on ischemia/reperfusion (I/R) injury of rat liver in which activated leukocytes play a critical role. DESIGN Prospective, randomized, controlled study. SETTING Research laboratory at a university(More)
We performed a study in spontaneous hypertensive rats (SHR) to determine whether carvedilol, a nonselective beta-adrenoceptor antagonist, activates capsaicin-sensitive sensory neurons (CSSNs), thereby promoting the release of calcitonin gene-related peptide (CGRP), a neuropeptide with an important role in maintenance of cardiovascular homeostasis.(More)
We previously reported that nitric oxide (NO) derived from endothelial NO synthase (NOS) increased endothelial prostacyclin (PGI(2)) production in rats subjected to hepatic ischemia-reperfusion (I/R). The present study was undertaken to determine whether neutrophil elastase (NE) decreases endothelial production of PGI(2), thereby contributing to the(More)
We examined whether resveratrol increases insulin-like growth factor-I (IGF-I) production in the hippocampus by stimulating sensory neurons in the gastrointestinal tract, thereby improving cognitive function in mice. Resveratrol increased calcitonin gene-related peptide (CGRP) release from dorsal root ganglion (DRG) neurons isolated from wild-type (WT)(More)
BACKGROUND & AIMS Sensory neurons play a critical role in reducing stress-induced gastric mucosal injury by releasing calcitonin gene-related peptide (CGRP) through an increase in gastric mucosal levels of prostacyclin (PGI(2)). Because estrogen enhances nerve growth factor-mediated CGRP production in sensory neurons, we hypothesized that stress-induced(More)