Risk Scoring System for Prognosis Estimation of Multivessel Disease Among Patients with ST-Segment Elevation Myocardial Infarction.

Multivessel disease (MVD) is an independent risk factor for poor prognosis in acute myocardial infarction patients. Although several global risk scoring systems (RSS) are in use in clinical practice, there is no dedicated RSS for MVD in ST-segment elevation myocardial infarction (STEMI). The primary objective of this study is to develop a novel RSS to estimate the prognosis of patients with MVD in STEMI.We used the Korean Acute Myocardial Infarction Registry (KAMIR) to identify 2,030 STEMI patients with MVD who underwent appropriate percutaneous coronary intervention (PCI). Their data were analyzed to develop a new RSS. The prognostic power of this RSS was validated with 2,556 STEMI patients with MVD in the Korean Working Group on Myocardial Infarction Registry (KORMI).Six prognostic factors related to all-cause death in STEMI patients with MVD were age, serum creatinine, Killip Class, lower body weight, decrease in left ventricular ejection fraction, and history of cerebrovascular disease. The RSS for all-cause death was constructed using these risk factors and their statistical weight. The RSS had appropriate performance (c-index: 0.72) in the KORMI validation cohort.We developed a novel RSS that estimates all-cause death in the year following discharge for patients with MVD in STEMI appropriately treated by PCI. This novel RSS was transformed into a simple linear risk score to yield a simplified estimate prognosis of MVD among STEMI patients.

Effects of SKI306X on arachidonate metabolism and other inflammatory mediators.

SKI306X was previously reported to have good anti-inflammatory and analgesic efficacy in various studies. To determine its mode of action, an investigation was carried out for some representative mediators. Arachidonic acid metabolism and its products are particularly important in inflammation and pain. The pro-inflammatory cytokines, especially interleukin-1 (IL-1) and tumor necrosis factor (TNF-alpha), and induced nitric oxide (NO) appear to be most involved in the inflammatory process such as osteoarthritis (OA). Thus SKI306X was tested to determine the effects on enzymes related to arachidonic acid metabolism and the release or synthesis of inflammatory mediators. SKI306X did inhibit the expression of cyclooxygenase-2 (COX-2) enzyme without affecting COX-1 and COX-2 activity. Leukotriene B4 (LTB4) production also was inhibited by SKI306X (IC50 = 98.7+/-4.26 microg/ml). SKI306X inhibited significantly TNF-alpha release (IC50 = 97.6+/-17.8 microg/ml) and NO production (IC50 = 280+/-17.8 microg/ml). But IL-1alpha release was not attenuated by SKI306X. This study suggests that inhibition of these mediators by SKI306X may be one of the mechanisms responsible for its anti-inflammatory effects.

SKI306X suppresses cartilage destruction and inhibits the production of matrix metalloproteinase in rabbit joint cartilage explant culture.

SKI306X was previously found to have cartilage protective effects in the experimental osteoarthritis (OA) model. To investigate the chondro-protective benefits of SKI306X for its capacity in altering changes in cartilage metabolism and molecular mechanisms of cartilage protective action, SKI306X is studied in rabbit cartilage explants culture. To investigate the protective effect of SKI306X on cartilage catabolism, we assessed collagen degradation in rabbit cartilage explants treated with interleukin-1alpha up to 3 weeks. To examine the reaction mechanism, matrix metalloproteinase (MMPs) were investigated by fluorimetric and Western blotting analysis. In addition, its effects on the activation process of proenzyme MMP-3 were determined by gelatin zymography. SKI306X significantly inhibited collagen degradation and inhibited the activities of several MMPs. Total MMPs activities in cultured medium were substantially increased in the third week at the time of collagen degradation with the absence of SKI306. However, the introduction of SKI306X decreased MMPs activities in cultured medium. Furthermore, Western blotting analysis proved that these inhibitory effects of this drug were the result of inhibiting MMPs expression. SKI306X also inhibited the activation of proenzyme MMP-3 to the active form of MMP-3. These results indicate that SKI306X inhibits matrix degradation by down regulating MMPs expression and secretion, inhibition of MMPs activity, and inhibiting activation of MMP-3 during the collagen breakdown process.

SKI306X, an oriental herbal mixture, suppresses gastric leukotriene B4 synthesis without causing mucosal injury and the diclofenac-induced gastric lesions.

SKI306X compound is a herbal mixture. This plant was in oriental medicine and was clinically approved for the treatment of osteoarthritis (OA) in Korea. SKI306X was previously found to have anti-inflammatory, analgesic and cartilage protective effects in several experimental models. In this study, SKI306X was investigated for its gastro-sparing effects on the gastric mucosa comparing with those of diclofenac, a conventional NSAID, and celecoxib, a cyclooxygenase-2 (COX-2) specific inhibitor. To investigate acute gastric damaging properties of SKI306X, the stomach of the animals was histologically and immuno-histochemically examined after single or repeated administration, and SKI306X demonstrated excellent gastric tolerability. SKI306X did not cause significant gastric irritation, erosion, or ulceration up to the orally administered dose of 2 g/kg and the intraperitoneal (i.p.) dose of 125 mg/kg. In contrast, diclofenac caused mucosal erosion, ulceration and bleeding at clinically effective doses. To determine the mode of gastro-sparing action, eicosanoid synthesis was examined in gastric mucosa and blood. SKI306X significantly decreased gastric and blood leukotriene B(4) (LTB(4)) production. However, SKI306X showed either no effect or a slight increase in levels of prostaglandin E(2) (PGE(2)). In addition, gastro-protective effects of SKI306X were exhibited by suppressing diclofenac-induced erosion and ulceration of gastric mucosa in a rat model and the possible mechanism of these effects were investigated. These studies demonstrated that SKI306X did not produce any significant damage up to dose of 2 g/kg and was effective in significantly protecting the damage associated to diclofenac-induced gastric ulcerations. SKI306X could spare the gastric mucosa through significantly suppressing gastric leukotriene (LT) synthesis.

Effects of gentianine on the production of pro-inflammatory cytokines in male Sprague-Dawley rats treated with lipopolysaccharide (LPS).

This study was undertaken to elucidate the mechanism of anti-inflammatory action of gentianine, a constituent of Gentiana Macrophylla. The effects of gentianine on lipopolysacharide (LPS)-induced production of pro-inflammatory cytokines were investigated in male Sprague-Dawley rats. For the first time, we found that oral administration of gentianine (10-100 mg/kg) suppressed the increases in tumor necrosis factor-alpha (TNF-alpha) (ED(50), 37.7 mg/kg) and interleukin (IL)-6 (ED(50), 38.5 mg/kg) in the sera from the rats challenged with bacterial LPS (100 microg/kg; i.p.). However, LPS induced production of other interleukins, such as IL-alpha, was not significantly altered by gentianine. These results suggest that the potential anti-inflammatory action of gentianine might be at least partly based on the suppressed production of TNF-alpha and IL-6.