云芝胞内糖肽口服制剂质量评价

目的：了解云芝胞内糖肽口服制剂的质量现状并发现存在的质量问题,完善质量标准,为药品监管提供技术支持。方法：从全国范围内抽取54批次云芝胞内糖肽口服制剂样品,依据现行质量标准检验,从药品安全性、有效性等方面进行探索性研究,建立多项检测方法全面分析其质量情况。结果及结论：云芝胞内糖肽口服制剂在原料工艺和制剂工艺中均发现与批准工艺不符的问题,其质量标准有待完善和提高。     

Improved synthesis of 5‐hydroxylysine (Hyl) derivatives*

Abstract: The synthesis of 5‐hydroxylysine (Hyl) derivatives for incorporation by solid‐phase methodologies presents numerous challenges. Hyl readily undergoes intramolecular lactone formation, and protected intermediates often have poor solubilities. The goals of this work were twofold: first, develop a convenient method for the synthesis of O‐protected Fmoc‐Hyl; secondly, evaluate the efficiency of methods for the synthesis of O‐glycosylated Fmoc‐Hyl. The 5‐O‐tert‐butyldimethylsilyl (TBDMS) fluoren‐9‐ylmethoxycarbonyl‐Hyl (Fmoc‐Hyl) derivative was conveniently prepared by the addition of tert‐butyldimethylsilyl trifluoromethanesulfonate to copper‐complexed Hyl[?‐tert‐butyloxycarbonyl (Boc)]. The complex was decomposed with Na⁺ Chelex resin and the Fmoc group added to the α‐amino group. Fmoc‐Hyl(?‐Boc, O‐TBDMS) was obtained in 67% overall yield and successfully used for the solid‐phase syntheses of 3 Hyl‐containing peptides. The preparation of Fmoc‐Hyl[?‐Boc, O‐(2,3,4,6‐tetra‐O‐acetyl‐β‐d ‐galactopyranosyl)] was compared for the thioglycoside, trichloroacetimidate and Koenigs–Knorr methods. The most efficient approach was found to be Koenigs–Knorr under inverse conditions, where Fmoc‐Hyl(?‐Boc)‐OBzl and peracetylated galactosyl bromide were added to silver trifluoromethanesulfonate in 1,2‐dichloroethane, resulting in a 45% isolated yield. Side‐reactions that occurred during previously described preparations of glycosylated Hyl derivatives, such as lactone formation, loss of side‐chain protecting groups, orthoester formation, or production of anomeric mixtures, were avoided here. Research on the enzymology of Lys hydroxylation and subsequent glycosylation, as well as the role of glycosylated Hyl in receptor recognition, will be greatly aided by the convenient and efficient synthetic methods developed here.     

Highly drug-resistant bacteria: Is intra- and inter-hospital communication optimal?

ObjectivesCommunication represents a key component of the control of highly drug-resistant bacteria (HDRB) in healthcare settings. This survey assessed communication strategies developed and adopted in a large hospital network.MethodsAn online survey was sent to 83 infection control specialists working in hospitals of the Pays de la Loire region, France, in June 2016. Internal and external systems of identification and communication of HDRB status (colonized and contact patients) were assessed at the following steps of the hospital pathway: patient admission, during the stay, at discharge, and at readmission.ResultsSixty-one hospitals (73%) participated in the survey: 31 (51%) had recently managed colonized patients and 51 (93%) had recently managed contact patients. At patient admission, 28 (46%) hospitals had an identification system for repatriated patients. During hospital stay, the colonized or contact status was informed in computerized patient records for 47/57 (82%) and 43 (75%) hospitals, respectively. At patient discharge, 56/61 (92%) hospitals declared transmitting the HDRB status to the downstream ward. Twenty-six and 25/60 (43% and 42%) hospitals had an automated alert system at readmission of colonized or contact patients, respectively. This strategy met the expectations of 15/61 (26%) infection control specialists.ConclusionEfforts are still required in terms of communication for HDRB control. Sharing experiences and tools developed by hospitals may be beneficial for the entire hospital network.     

薄芝糖肽抑制大鼠实验性癫痫发作及其机制研究

目的研究薄芝糖肽对大鼠癫痫发作的抑制作用及对免疫指标的影响。方法 30只SD大鼠分为空白组、模型组、薄芝糖肽组,以腹腔注射青霉素的方法制作大鼠癫痫模型,注射前60 min模型组经尾静脉给予生理盐水2 mL,薄芝糖肽组经尾静脉给予薄芝糖肽2 mL(含5 mg多糖,1 mg多肽)。观察各组大鼠行为,描记脑电图,测定T淋巴细胞亚群和血清免疫球蛋白浓度。结果薄芝糖肽组痫性发作程度较模型组明显减轻(p<0.05)。薄芝糖肽组出现痫样波形的潜伏时间延长,频率降慢、幅度降低。模型组致痫后免疫系统出现抑制现象,薄芝糖肽组大鼠的免疫指标较模型组有明显的提升(p<0.05)。结论薄芝糖肽可抑制大鼠癫痫发作,其机制可能与薄芝糖肽可以明显恢复大鼠免疫指标有关。     

云芝糖肽对大鼠免疫功能的影响

研究了彩绒革盖菌(Coriolus versicolor)中提取的云芝糖肽(Polysaccharides peptides,PSP)对大鼠免疫功能的影响。大鼠连续口服PSP2,0g/kg/d可促进淋巴细胞转化,血清IgG滴度明显升高。此外,还可取消大鼠隔天口服环磷酰胺40mg/kg对自然杀伤细胞功能的抑制。结果提示,口服PSP2.Og/kg/d可明显提高大鼠细胞免疫和体液免疫功能。     

A multicentre study:Staphylococcus andEnterococcus susceptibility to antibiotics

A multicentre study to evaluate the susceptibility of Gram-positive cocci isolated from clinical samples, was performed by six centres working in different areas of Italy. We examined 4,544 strainsof Staphylococcus aureus, 4,381 strains of coagulase-negative staphylococci and 2,478 strains of enterococci. The following antibiotics were tested: penicillin G, ampicillin, amoxicillin, piperacillin, imipenem, oxacillin, ofloxacin, pefloxacin, ciprofloxacin, gentamicin, tobramycin, amikacin, netilmicin, rifampicin, clindamycin, tetracycline, cotrimoxazole, erythromycin, chloramphenicol, vancomycin and teicoplanin. Oxacillin-susceptible staphylococci confirmed their susceptibility to many other antimicrobial agents while oxacillin-resistant strains confirmed their multiple and frequent resistance to antibiotics. Resistance to oxacillin, cotrimoxazole and chloramphenicol was more frequent in coagulase-negative staphylococci than inStaphylococcus aureus. Aminoglycosides, rifampicin and quinolones were more active against coagulase-negative staphylococci than againstStaphylococcus aureus. Enterococci were susceptible to penicillins and imipenem, and moderately susceptible to cipro-floxacin. Susceptibility of 70–79% was observed with high levels of aminoglycosides. Excellent results against staphylococci and enterococci were observed with vancomycin and teicoplanin.     

Synthesis and purification of two SP (6–11) analogues with enhanced selectivity for the NK-1 receptor

Two hexapeptide analogues of Substance P (6–11) have been synthesized. Replacement of Gly₉ by proline provides a peptide with tenfold enhanced selectivity for the NK-1 receptor. The corresponding proline-containing glycopeptide incorporating a β-d -glucopyranosyl residue linked to the side-chain of Glus was 100 times more selective than Substance P for the same receptor.     

Synthetic TN glycopeptide related to human glycophorin A.M†

Three 2-acetamido-2-deoxy-α-d -galactopyranoses attached to Ser², Thr³ Thr⁴ of the amino-terminal portion of glycophorin A^M are responsible for the so-called T_N blood group specificity. The corresponding glycopeptide H₂N-Ser-Se*r-Th*r-Th*r-Gly-OH obtained by a stepwise peptide coupling strategy was submitted to a detailed high-field nuclear magnetic resonance (n.m.r.) analysis. ¹³C-n.m.r. spectrum confirms the validity of previous assignments made on M sialo and asialoglycopeptides obtained by specific degradation of human glycophorin A^M. In addition, the 400 MHz ¹H-n.m.r. spectrum allowed most of the proton resonances to be assigned. A careful examination of the chemical shifts and coupling constants revealed some interesting features of the conformational properties of the GalNAc-Ser and GalNAc-Thr linkage as well as of the rotational isomerism of Thr and Ser side-chains. The data give conclusive evidence that high-field n.m.r. spectroscopy can be successfully used to gain structural and dynamic information on rather sophisticated glycopeptides.     

人参糖肽的降血糖作用(英文)

目的:研究人参糖肽降血糖作用。方法:观察人参糖肽对正常小鼠或家兔以及由四氧嘧啶和链尿菌素引起高血糖大鼠或小鼠的降血糖作用。血糖和肝糖元含量分别用显色剂邻甲苯胺和碘试剂呈色后,用分光光度计测定。结果:给正常小鼠ip或sc人参糖肽(50,100和200mg/kg)或按30和60mg/g剂量给正常家兔im人参糖肽,能明显降低正常动物的血糖和肝糖元,并且有剂量依赖关系;人参糖肽降血糖作用可持续16h;其次,人参糖肽对实验性高血糖动物也有明显的降血糖活性。结论:注射人参糖肽无论对正常动物还是高血糖动物都有明显的降低血糖和肝糖元作用。     

Synthesis and biological activity of the mono- and di-galactosyl-vespulakinin 1 analogues

Syntheses are described of some mono- and di-glycosylated analogues of vespulakinin 1. The solid phase procedure, based on the Fmoc chemistry, was used to prepare (Gal α)Thr³-vespulakinin 1, (Galβ)Thr³-vespulakinin 1 and the di-glycosylated analogue ((Gal α)Thr³. (Gal α)Thr⁴-vespulakinin 1. The β-glycosylated derivative was also prepared by the continuous flow variant of the Fmoc polyamide method. The synthesized glycopeptides were purified and characterized by amino acid analysis, optical rotation, analytical HPLC, ¹H-and ¹³C-NMR and FAB-MS. Preliminary pharmacological experiments showed that the carbohydrate-free vespulakinin 1 is less active than bradykinin (about 0.3 times on a molar basis) when tested by guinea pig rectum contraction, and the two monoglycosylated analogues are equiactive (about 0.9 times the bradykinin activity). The most active derivative, the (Gal α)Thr³, (Gal α)Thr⁴-vespulakinin 1 analogue, was about 2.5 times as active as bradykinin.