开心散及其各单药成分的肠吸收研究

目的:采用改良外翻肠囊模型,研究开心散复方及各单药的肠吸收情况。方法:利用翻转肠囊法建立开心散复方及各单药的大鼠肠吸收模型,并用HPLC、HPLC-MS法检测开心散及其各单药的肠吸收成分。结果:HPLCDAD检测器条件下可测得开心散复方中主要吸收入肠成分是远志中的成分,未检测到人参、茯苓、石菖蒲的肠吸收成分。多级质谱研究表明开心散复方和远志中主要的可吸收成分为寡糖酯类化合物。结论:HPLCDAD检测条件下,发现开心散肠吸收的主要成分是远志中的寡糖酯类成分,但这些成分的化学结构及人参、茯苓、石菖蒲的肠吸收成分需进一步研究。     

Pharmacokinetics,distribution, and excretion of sodium oligomannate,a recently approved anti-Alzheimer's disease drug in China

The National Medical Products Administration has authorized sodium oligomannate for treating mild-to-moderate Alzheimer's disease. In this study, an LC-MS/MS method was developed and validated to quantitate sodium oligomannate in different biomatrices. The plasma pharmacokinetics, tissue distribution, and excretion of sodium oligomannate in Sprague-Dawley rats and beagle dogs were systematically investigated. Despite its complicated structural composition, the absorption, distribution, metabolism, and excretion profiles of the oligosaccharides in sodium oligomannate of different sizes and terminal derivatives were indiscriminate. Sodium oligomannate mainly crossed the gastrointestinal epithelium through paracellular transport following oral administration, with very low oral bioavailability in rats (0.6%–1.6%) and dogs (4.5%–9.3%). Absorbed sodium oligomannate mainly resided in circulating body fluids in free form with minimal distribution into erythrocytes and major tissues. Sodium oligomannate could penetrate the blood-cerebrospinal fluid (CSF) barrier of rats, showing a constant area under the concentration-time curve ratio (CSF/plasma) of approximately 5%. The cumulative urinary excretion of sodium oligomannate was commensurate with its oral bioavailability, supporting that excretion was predominantly renal, whereas no obvious biliary secretion was observed following a single oral dose to bile duct-cannulated rats. Moreover, only 33.7% (male) and 26.3% (female) of the oral dose were recovered in the rat excreta within 96 h following a single oral administration, suggesting that the intestinal flora may have ingested a portion of unabsorbed sodium oligomannate as a nutrient.     

狗枣猕猴桃寡糖的免疫调节作用

本文报道了从狗枣猕猴桃的根中提取的寡糖(简称AKOS)对小鼠免疫功能的调节作用。小鼠皮下注射AKOS,1～2w后分别测定免疫功能。结果:①AKOS能刺激抗体形成细胞的增生,并对醋酸氢化可地松的免疫抑制有拮抗作用;②能加强巨噬细胞的吞噬功能;③能增强由分裂原诱导的淋巴细胞增殖反应。结果表明AKOS是一种有效的免疫调节剂,对于增强机体的免疫功能具有一定的意义。     

Fructooligosaccharides exhibit more rapid fermentation than long-chain inulin in an in vitro fermentation system

This study investigated how chain length affects fermentation properties of fructooligosaccharides (FOSs) and inulin (IN). Chain lengths of FOSs and IN vary from an average degree of polymerization (DP) of 3 to greater than 20. Three samples classified as FOSs (samples A, B, and C) and 3 samples classified as IN (samples D, E, and F) were fermented via an in vitro batch method with human fecal inoculum as the source of microbes. Samples were removed at 0, 4, 8, 12, and 24 hours for total short-chain fatty acid (SCFA), acetate, propionate, and butyrate measurement via gas chromatography. Sample chain length did not affect SCFA concentrations in a predictable manner. Sample E (90%-94% DP > 10, 6%-10% DP = 1-2), a mixture of long-chain IN and short-chain FOS, produced significantly more total SCFA and acetate than the other samples. Sample F (DP > 20), the longest-chain IN, produced the lowest concentration of butyrate at 24 hours. The rate of FOS fermentation was higher than IN fermentation during 0 to 4 hours for all SCFAs, and the rate of IN fermentation was higher than FOS fermentation during 12 to 24 hours for all SCFAs. Chain length affects in vitro fermentability, with short chains being rapidly fermented and long chains being steadily fermented. Clinical studies should follow this work to verify if these differences exist in vivo.     

A tube-fed liquid formula diet containing dietary fiber increased stool weight in bed-ridden elderly patients

OBJECTIVE: The number of bedridden elderly patients who need a liquid diet has been increasing. We evaluated the usefulness of a tube-fed liquid diet containing cellulose and oligosaccharide for elderly bedridden patients. METHODS: Twenty-two elderly bedridden patients were given a liquid diet containing cellulose and lafinose for 4 wk. Parameters associated with blood and stool weight were measured during this period. RESULTS: Stool weight increased by 32.0 g in men and 8.8 g in women at 2 wk and remained at these weights up to 4 wk (P < 0.05 before and after 2 wk, 3 wk, and 4 wk in men, and P < 0.05 before and after 3 wk in women). Body weight increased in men (0.5 kg) and women (0.7 kg) 15 d after starting the diet and then remained at these values up to 29 d thereafter, and statistically significant differences were not seen. There were no changes in nutritional parameters such as total protein. CONCLUSION: No significant changes were observed in the general condition of elderly patients, with the exception of a positive increase in fecal weight, by 30-d supplementation of a liquid diet containing cellulose and lafinose.     

Antimicrobial Activity of SCH 27899, Oligosaccharide Member of the Everninomycin Class with a Wide Gram-Positive Spectrum

The in vitro antimicrobial activity of SCH 27899 (everninomycin), a novel oligosaccharide compound of the everninomycin class, was compared with vancomycin, chloramphenicol, clinafloxacin, teicoplanin and doxycycline against 428 clinical strains of bacteria. Everninomycin base exhibited the greatest antimicrobial activity compared to other formulations against all strains tested (MIC₉₀: 0.25 μ/ml) followed by clinafloxacin and teicoplanin (MIC₉₀: 0.5 μg/ml), vancomycin (MIC₉₀: 2 μg/ml), and doxycycline (MIC₉₀: 16 μg/ml). Everninomycin demonstrated the best activity against Streptococcus spp. (serogroups A, B, C, F, G) and Streptococcus pneumoniae , and lower activity against coagulase-negative staphylococci (MIC₉₀: 0.5 μg/ml). All enterococci had an everninomycin MIC of 0.5 μg/ml or less. Everninomycin had no measurable antimicrobial activity against gram-negative aerobic organisms except Flavo-bacterium meningosepticum (MIC₅₀: 2 μg/ml). Some everninomycin activity was observed against Clostridium spp., Peptostreptococcus spp., and the Prevotella bivius-disiens group. Everninomycin showed excellent activity (MIC₉₀: 0.25 μg/ml) against the fluoroquinolone-resistant strains and all gram-positive strains resistant to vancomycin (MICs 4 μg/ml). The MBC/MIC ratios and killing curve data suggest that everninomycin is not uniformly or rapidly bactericidal. These in vitro data indicate that everninomycin could be useful against emerging gram-positive strains resistant to other contemporary antimicrobials.     

Metabolism: Enzymatic Diagnosis of Mucopolysaccharidosis and Lipidosis

New radiolabeled oligosaccharides were prepared from various glycosaminogly-cans for the purpose of diagnosis of mucopolysaccharidosis and glycosphingoli-pidosis and of differentiation of enzymatic heterogeneity. Hunter syndrome hemizygote and heterozygote could be successfully diagnosed using hair roots as an enzyme source. The deficiency of galactose-6-sulfate sulfatase was observed in Morquio syndrome in addition to the deficiency of N-acetyl-galactosamine-6-sulfate sulfatase. Tay-Sachs disease was diagnosed without separation of hexosaminidase using hyaluronic acid-derived trisaccharide as sub-strate, Trisaccharide substrate derived from keratan sulfate could be used for the diganosis of G_M1-gangliosidosis, however, it was not useful for the dif-ferentiation of type 1 and type 2.     

Effects of SCH27899 (Ziracin), an oligosaccharide everninomicin antibiotic,on urate kinetics in humans

Objective Intravenous administration of an everninomicin antibiotic, SCH27899 (Ziracin), in healthy subjects caused a marked decrease in serum urate by increasing its urinary excretion, as well as an increase in serum bilirubin in a dose-dependent manner. To clarify the underlying mechanism, a crossover study and an in vitro study were conducted.Methods Crossover study was performed in nine healthy male volunteers over three periods by administering SCH27899 (1-h i.v. infusion of 3 mg/kg) alone, probenecid (2000 mg, p.o.) alone and their combination. Also, an in vitro experiment was conducted using rat brush-border membrane vesicles to elucidate the effect of SCH27899 on urate transport across renal tubular epithelium.Results SCH27899 alone and probenecid alone showed a uricosuric, serum urate-lowering effect, and, when given in combination, the effects on serum urate appeared to be additive, as indicated in the earlier phase, prior to the peaks of respective drug effects. Serum and urinary concentrations of SCH27899 were not influenced by the co-administration of probenecid. Serum bilirubin was also significantly increased by both SCH27899 alone and in combination with probenecid. The SCH27899–probenecid combination additive effect on serum bilirubin did not reach significance. SCH27899, probenecid and losartan, an angiotensin-II-receptor antagonist possessing a uricosuric effect, significantly inhibited ¹⁴C-urate uptake into the vesicles, which was dependent on the pH gradient across the membrane; whereas, vancomycin did not.Conclusion It is concluded that SCH27899 itself contributes, at least in part, to a uricosuric effect following i.v. infusion. However, some metabolite(s) may also contribute to this, since the degree of urate-uptake inhibition by SCH27899 was less than probenecid and losartan, and the serum urate-lowering effect was delayed and prolonged compared with the time profile of serum concentration.     

Distinct host range of influenza H3N2 virus isolates in Vero and MDCK cells is determined by cell specific glycosylation pattern

Influenza A viruses were isolated in Vero, MDCK cells and chicken embryos. In contrast to MDCK-derived variants all H3N2 isolates obtained in Vero cells neither agglutinated chicken erythrocytes nor grew in chicken eggs. These host range differences of H3N2 Vero and MDCK isolates were noticed even in the absence of amino acid substitutions in the HA1 molecule. Evaluation of HA glycosylation pattern by treatment with endoglycosidases H and F revealed that Vero-variants contained more oligosaccharides of the high mannose type than did the corresponding MDCK-isolates. Removal of some mannose residues from the non-reducing termini of the carbohydrates by exomannosidase treatment resulted in the ability of Vero-isolates to agglutinate chicken erythrocytes. Glycosylation pattern and properties of H3N2 viruses grown in Vero cells were close to those of viruses grown in human kidney epithelial cells, whereas the H1N1 variants isolated from Vero, MDCK cells or eggs did not differ in agglutination properties, carbohydrate composition or ability to infect eggs.