The level of plasma diamine oxidase (DAO) activity is associated with the maturation and integrity of small intestinal mucosa. This study in rats investigated whether a decreased level of plasma DAO could reflect the severity of mucosal injury due to intravenous 5-fluorouracil (5-FU) treatment. The beneficial effect of soluble dietary fiber (SDF) on preventing diarrhea after 5-FU treatment was also examined. To induce diarrhea, 5-FU (50 mg/kg/day for four days) was administered via the tail vein with or without SDF supplementation. After 5-FU treatment, the majority of rats developed moderate to severe diarrhea, and levels of plasma DAO activity significantly decreased compared to those of control group (P < 0.05). Scanning electron microscopy revealed disarrangement of the small intestinal villi. Contrarily, the rats supplemented with SDF had diarrhea less frequently (50.0 vs. 91.7 %, P = 0.025) on day five, and DAO activity levels were significantly higher than in those rats administered 5-FU alone (8.25 ± 5.34 vs. 5.50 ± 4.32, P = 0.023). In conclusion, plasma DAO activity decreases in response to severe intestinal mucosal injury after 5-FU treatment, and SDF supplementation might be a practical and useful treatment for reducing the intestinal toxicity of 5-FU.

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MIE significantly attenuated postoperative serum CRP levels compared with OE. MIE could contribute to improved survival.

ContextYokukansan (YKS) is a traditional Japanese herbal medicine called kampo medicine in Japan. Its extract comprises seven crude drugs: Atractylodis lanceae rhizoma, Poria, Cnidii rhizoma, Uncariae uncis cum ramulus, Angelicae radix, Bupleuri radix, and Glycyrrhizae radix. YKS is used to treat neurosis, insomnia, as well as behavioral and psychological symptoms of dementia.ObjectiveTo confirm the exposure and pharmacokinetics of the active components of YKS in healthy volunteers.Design, Setting, and ParticipantsA randomized, open-label, 3-arm, 3-period, crossover trial was conducted on 21 healthy Japanese volunteers at the Kochi Medical University between May 2012 and November 2012.InterventionsSingle oral administration of YKS (2.5 g, 5.0 g, or 7.5 g/day) during each period.Main Outcome MeasurePlasma concentrations of three active compounds in YKS, namely 18β-glycyrrhetinic acid (GA), geissoschizine methyl ether (GM), and hirsuteine (HTE).ResultsThe mean maximum plasma concentrations (Cmax) of GM and HTE increased dose-dependently (ranges: 0.650–1.98 ng/mL and 0.138–0.450 ng/mL, respectively). The times to maximum plasma concentration after drug administration (t max) were 0.500 h for GM and 0.975–1.00 h for HTE. The apparent elimination half-lives (t 1/2) were 1.72–1.95 h for GM and 2.47–3.03 h for HTE. These data indicate the rapid absorption and elimination of GM and HTE. On the other hand, the C max, t max, and t 1/2 of GA were 57.7–108 ng/mL, 8.00–8.01 h, and 9.39–12.3 h, respectively.ConclusionWe demonstrated that pharmacologically active components of YKS are detected in humans. Further, we determined the pharmacokinetics of GM, HTE, and GA. This information will be useful to elucidate the pharmacological effects of YKS.Trial RegistrationJapan Pharmaceutical Information Center JAPIC CTI-121811

The CCI was significantly correlated with the prognosis of esophageal cancer patients who underwent curative-intent esophagectomy.