Hirokazu Ueno

Nicotine enhances human vascular endothelial cell expression of ICAM-1 and VCAM-1 via protein kinase C, p38 mitogen-activated protein kinase, NF-κB, and AP-1

Investigation into the etiology of atherosclerosis has identified cigarette smoking as a major risk factor. Although it has been established that cellular adhesion molecule expression on endothelial cells is stimulated by nicotine, the mechanism by which this occurs is not clear. The aim of this study was to determine the effect of nicotine on the expression of the adhesion molecules, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 inendothelial cells and to determine the involvement of imporcule tank known intermediaries, protein kinase C (PKC), p38 mitogen-activated protein kinase (p38 MAPK), and the transcription factors NF-κB and AP-1. Human umbilical vein endothelial cells (HUVEC) were exposed to 10−8M nicotine for up to 24 h. Expression of ICAM-1 and VCAM-1 and phosphorylation of p38 were examined by immunoblot. Electrophoretic mobility shift assay was performed to determine NF-κB and AP-1 activation. We observed that nicotine increased the expression of ICAM-1 and VCAM-1 with a peak at 6h.p38 MAPK was activated after 5 min exposure to 10−8 mol/L nicotine and returned to baseline levels by 30 min. Exposure of HUVEC to nicotine resulted in a 4.1-fold increase of PKC activity at 5 min, which subsequently returned to control levels by 15 min. Nicotine (10−8 mol/L) also increased NF-κB and AP-1 activity. Inhibitors of p38 MAPK, PKC, and NF-κB suppressed nicotine-stimulated expression of ICAM-1 and VCAM-1. Our results indicate that nicotine enhances the expression of ICAM-1 and VCAM-1 on the endothelial cell surface via a second messenger pathway which involves PKC and p38 MAPK-mediated activation of NF-κB and AP-1, resulting in increased expression of these cellular adhesion molecules.

Cellular injury score for multiple organ failure severity scoring system.

BACKGROUND Cellular Injury Score (CIS) is an index of cellular injury, being calculated from three parameters of intracellular metabolism: arterial ketone body ratio, osmolality gap, and blood lactate. METHODS The usefulness of CIS as a severity scoring system for patients with multiple organ failure was prospectively evaluated in 157 consecutive patients with MOF (58 survivors, 99 nonsurvivors). RESULTS CISs in nonsurvivors were significantly higher compared with those in survivors throughout the clinical courses. CIS was significantly correlated with the number of failing organs and mortality rate. The optimal cutoff point of CIS from receiver operating characteristics curve analysis was 4 for the maximal value during the clinical course. The changes in CIS well reflected the severity of injury in survivors and nonsurvivors who died within 2 weeks. CONCLUSION CIS could be a useful index for mortality risk prediction and is potentially applicable as a severity scoring system for individual patients with MOF.

Partial liquid ventilation with FC-77 suppresses the release of lipid mediators in rat acute lung injury model.

Objective:To investigate whether the release of lipid mediators is suppressed in rats with experimentally induced acute lung injury managed with partial liquid ventilation (PLV) using FC-77. Design:Prospective, randomized controlled study. Setting:Research laboratory in a university. Subjects:Male Sprague-Dawley rats. Interventions:After tracheostomy was performed under general anesthesia, lung injury was induced by intratracheal instillation of HCl. The PLV group was then subjected to conventional gas ventilation for 30 mins, followed by PLV using FC-77. The control group was subjected to conventional gas ventilation throughout the study period. Measurements and Main Results:In the PLV group the following results were obtained: a) impaired oxygenation was markedly improved; b) the increase in the serum levels of lipid mediators such as leukotriene B4, thromboxane A2, and 6-keto-prostaglandin F1&agr; was suppressed; and c) the increase in the concentrations of leukotriene B4, thromboxane A2, and 6-keto-prostaglandin F1&agr; in the total lung homogenate at 180 mins after lung injury was also suppressed. Conclusion:This study indicates that PLV using FC-77 suppresses the release of lipid mediators in our rat model of acute lung injury. However, further investigation is needed to clarify the precise mechanism of this effect.

Nutritional Support for the Patient with Multiple Organ Failure in Gastroenterological Surgery.

消化器外科領域の多臓器不全 (multiple organ failure;MOF) 70例を対象に, いかにして代謝動態を把握し, いかなる栄養管理を施行すればよいかを検討した.代謝動態の把握には, indirect calorimetryによるエネルギ-消費量, respiratory quotient, %FAT, 動脈血中ケトン体比 (arterial ketone body ratio; AKBR) およびケトン体量, 血中乳酸値などが有効であった.MOF患者はhypermetabolicで, 基礎エネルギー消費量の140～150%を消費しており, AKBRの低下している肝不全合併MOF症例では, エネルギー基質の利用制限や蛋白代謝の低下が観察された.全症例に対して中心静脈栄養法を施行した.消費エネルギー量相当のエネルギ-量の投与は肝不全合併MOFおよび腎不全合併MOFで困難であったが, 前者ではATP-Mgやplasma exchangeの併用が, 後者では持続的血液濾過や持続的血液濾過透析の併用が有効であった.また分枝鎖アミノ酸を多量に含む製剤は有用であった.