Biological & pharmaceutical bulletin
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The aim of this study was to explore the relationship and interpret the clinical importance of acute physiology and chronic health evaluation III (APACHE III) and levels of cytokines in patients with systemic inflammatory response syndrome (SIRS) after coronary artery bypass grafting (CABG) with or without cardio-pulmonary bypass (CPB) to see if they are beneficial for evaluating the seriousness of SIRS. The data suggested that the APACHE III score and levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and soluble interleukin-2 receptor (sIL-2R) were significantly higher after conventional CABG (CCABG) than after off-pump coronary artery bypass grafting (OPCAB) (p<0.05). With an increase in the APACHE III score, the levels of IL6, IL8, TNF-alpha, IL-1beta, and sIL-2R and the morbidity of multiple organ dysfunction syndrome (MODS) increased gradually (p<0.01), while the level of IL2 decreased (p<0.01). ⋯ In conclusion, despite comparable surgical trauma, we believe that CPB is one of the most important factors responsible for stimulating an inflammatory response. SIRS after OPCAB was clearly mitigated compared with CCABG. Determination of the APACHE III score and plasma IL-1beta, IL6, IL8 and sIL-2R concentrations might be helpful for evaluating the severity of SIRS following CABG and making a prognosis.
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Glycyrrhizae radix is used to treat abdominal pain as a component of shakuyakukanzoto (shaoyao-gancao-tang), a traditional Chinese medicine formulation. Previously, we have reported the isolation of glycycoumarin as a potent antispasmodic with an IC50 value of 2.93+/-0.94 microM for carbamylcholine (CCh)-induced contraction of mouse jejunum from an aqueous extract of Glycyrrhizae radix (licorice), and clarified that its mechanism of action involves inhibition of phosphodiesterase 3. The purpose of the present study was to examine an antispasmodic principle of licorice other than glycycoumarin. ⋯ At the time, the relaxant activity of the treated sample was increased significantly, shifting the IC50 from 358+/-104 to 150+/-38 microg/ml for CCh-induced contraction. Isoliquiritigenin also showed the most potent inhibition of mouse rectal contraction induced by CCh with an IC50 value of 1.70+/-0.07 microM. These results suggest that isoliquiritigenin acts as a potent relaxant in the lower part of the intestine by transformation from its glycosides.
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Clinical Trial
Pharmacokinetics/pharmacodynamics of acetaminophen analgesia in Japanese patients with chronic pain.
Acetaminophen (APAP) is a popular analgesic. In the present study, we characterized the pharmacokinetics and pharmacodynamics of APAP in the Japanese. Five healthy volunteers were administered 1000 mg of APAP orally. ⋯ The pharmacokinetic and pharmacodynamic parameter (mean+/-S. D.) estimates were as follows: clearance, 18.7+/-4.7 l/h; distribution volume, 30.9+/-6.8 l; absorption rate constant, 2.4+/-1.3 h(-1); rate constant for the elimination of APAP from the effect compartment, 1.3+/-0.5 h(-1); maximum pain relief score, 4.6+/-2.2 units; effect compartment concentration at 50% maximum, 2.0+/-1.2 microg/ml; and sigmoid factor, 1.3+/-0.7. These results suggest that these parameters can be used to determine an effective APAP dosage regimen for Japanese patients with chronic pain.
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In China, the collection of wild Glycyrrhiza uralensis, one of the raw materials of Chinese licorice, has been restricted to prevent desertification. To compensate for the reduced supply of wild Glycyrrhiza plants, cultivation programs of G. uralensis have been initiated in eastern Inner Mongolia. ⋯ In addition, glycycoumarin content, which is an antispasmodic and species-specific ingredient of G. uralensis, was similar when comparing the boiled water extracts of 4-year-old cultivated roots and licorice (0.10+/-0.02% vs. 0.10+/-0.06%). These data suggest that cultivated G. uralensis roots may be an adequate replacement for the generation of licorice in the context of the restriction of wild Glycyrrhiza plant collection.
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We compared particulate and microbial contamination in residual solutions of peripheral intravenous admixtures after the termination of drip infusion between intravenous fluids admixed with glass ampoule drugs and those admixed with pre-filled syringe drugs. The mean number of particles>or=1.3 microm in diameter per 1 ml of residual solution was 758.4 for fluids (n=60) admixed with potassium chloride in a glass ampoule (20 ml volume), 158.6 for fluids (n=63) admixed with potassium chloride in a pre-filled syringe (20 ml volume), 736.5 for fluids (n=66) admixed with sodium chloride in a glass ampoule (20 ml volume), 179.2 for fluids (n=15) admixed with sodium chloride in a pre-filled syringe (20 ml volume), 1884.5 in fluids (n=30) admixed with dobutamine hydrochloride in 3 glass ampoules (5 ml volume), and 178.9 (n=10) in diluted dobutamine hydrochloride in pre-filled syringes (50 ml volume: For these samples alone, particulate and microbial contamination were evaluated in sealed products.) Thus, for potassium chloride or sodium chloride for injection, the number of particles>or=1.3 microm in diameter in the residual intravenous solution was significantly higher for fluids admixed with glass ampoule drugs than for those admixed with pre-filled syringe drugs (p<0.0001). ⋯ Therefore, for the prevention of glass particle contamination in peripheral intravenous admixtures, the use of pre-filled syringe drugs may a useful method. No microbial contamination was observed in any of the residual solutions of 5 types of admixture.