Anti-inflammatory effects of LK-3, on LPS-induced sepsis in rats.

Dextromethorphan (DM), an antitussive agent, has been shown to have anti-inflammatory and immunomodulatory effects in vitro. Thus, the aim of this study was to evaluate the effects of LK-3, an analog of DM, on sepsis induced by intravenous (i.v.) administration of lipopolysaccharide (LPS; 10 mg/ kg) in anesthetized Wistar rats. Results demonstrated that post-treatment with LK-3 (4 mg/kg, i.v.) significantly attenuated the deleterious hemodynamic changes (e.g., hypotension and bradycardia) in rats treated with LPS. Meanwhile, LK-3 (4 mg/kg) significantly inhibited the elevation of plasma tumor necrosis factor-alpha, as well as values of glutamate-oxalacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) caused by LPS. The induction of inducible NO synthase and the overproduction of NO and superoxide anions by LPS were also reduced by post-treatment of LK-3. Moreover, infiltration of neutrophils into the lungs and liver of rats 8 h after treatment with LPS was also reduced by post-treatment with LK-3. In conclusion, the beneficial effects of LK-3 on LPS-induced sepsis resulted from its anti-inflammatory and antioxidant effects.

Hemodynamic significance of heart rate in neurally mediated syncope.

BACKGROUND: Vasovagal and vasodepressor syncope are used interchangeably in the literature to describe the common faint syndrome, now collectively named neurally mediated syncope. The significance of heart rate (HR) in these reflex-induced reactions remains unclear. HYPOTHESIS: The study was undertaken to investigate the hemodynamic significance of HR in tilt-induced neurally mediated syncope. METHODS: In all, 113 patients with syncope of unknown etiology were studied by head-up tilt test with invasive hemodynamic monitoring. Thirty-five patients (15 women, 20 men, age range 21 to 72 years) developed syncope and were enrolled for analysis. The hemodynamic data were compared between patients who developed bradycardia (vasovagal group, n = 15) and those without bradycardia (vasodepressor group, n = 20). RESULTS: The baseline hemodynamic data (mean +/- standard deviation) and the hemodynamic responses after 10-min headup tilt were similar between patients in the vasovagal and vasodepressor groups. During syncope, patients with vasovagal reaction developed hypotension and paradoxical bradycardia (HR = 52.4 +/- 5.9 beats/min), while patients with vasodepressor reaction developed a precipitous drop in arterial blood pressure with inappropriate HR (105 +/- 21 beats/min) compensation. Patients with vasovagal syncope manifested a significantly lower cardiac index and a significantly higher systemic vascular resistance index than patients with vasodepressor syncope (1.47 +/- 0.29 vs. 1.97 +/- 0.41 1/min/m2, p < 0.001 and 2098 +/- 615 vs. 1573 +/- 353 dynes x s x cm(-5) x m2, p < 0.003, respectively). A positive correlation existed between HR and cardiac index (r = 0.44, p = 0.008) during syncope in the patients studied. CONCLUSIONS: These findings suggest that the hemodynamic characteristics of vasovagal and vasodepressor reactions are different, and that HR plays a significant role in neurally mediated syncope.

Hepatic effects among workers exposed to ethylene glycol monoethyl ether acetate.

Data about hepatic effects of ethylene glycol ethers had been limited and inconsistent. In this study, we determined whether ethylene glycol monoethyl ether acetate (EGEEA) was a hepatotoxin in exposed workers. Workers from one silk-screening shop (n=29), using EGEEA as the major cleaning solvent, were recruited as high exposure group. Another group of workers with indirect and low exposure to EGEEA (n=57) were selected as the comparison group. Air concentration of EGEEA was measured by 8-h personal sampling. The mean of air EGEEA concentration in the high exposure group was 7.41-16.5 ppm. The mean of air EGEEA concentration in the low exposure group was 0.07-3.62 ppm. Liver function profiles showed that the AST, ALT, ALP and gamma GT in both male and female EGEEA-exposed workers were not significantly different from those in the comparison group. After adjustment for potential confounders such as gender, body mass index, hepatitis B status, and duration of employment, no difference in hepatic dysfunction were found between exposed and comparison groups. In addition, a two-year follow-up study of these EGEEA-exposed workers, no significant change in hepatic function was noted either. The findings suggest that EGEEA is not a hepatotoxin in this workplace.

Beneficial effects of LK-4, an analog of dextromethorphan on lipopolysaccharide-induced sepsis in rats.

Dextromethorphan (DM), an anti-tussive agent, has been claimed to have anti-inflammatory and immunomodulatory effects in vitro. In our preliminary screening test, LK-4, an analog of DM, can afford more protection against circulatory failure induced by LPS than that of DM. Thus, the aim of this study was to evaluate the effects of LK-4 on sepsis induced by intravenous (i.v.) administration of lipopolysaccharide (LPS; 10 mg/kg) in anesthetized Wistar rats and survival rate by intraperitoneal administration of LPS (70 mg/kg) in conscious ICR mice. Results demonstrated that posttreatment with LK-4 (3 and 5 mg/kg, i.v.) significantly attenuated the deleterious hemodynamic changes (e.g., hypotension and tachycardia) in rats treated with LPS. Meanwhile, LK-4 (3 mg/kg) significantly inhibited the elevation of plasma tumor necrosis factor-alpha, as well as values of GOT and GPT, and BUN and creatinine caused by LPS. The induction of inducible NO synthase and the overproduction of NO and superoxide anions by LPS were also reduced by LK-4. Moreover, infiltration of neutrophils into the lungs and liver of rats 8 h after treatment with LPS was also reduced by LK-4. Furthermore, LK-4 increased the survival rate of mice insulted by toxic dose of LPS. In conclusion, the beneficial effects of LK-4 on LPS-induced sepsis result from its anti-inflammatory and anti-oxidant effects. Thus, LK-4 can be potentially used as a therapeutic agent for sepsis in the future.