Preparation of protected peptidyl thioester intermediates for native chemical ligation by Nα‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry: considerations of side‐chain and backbone anchoring strategies,and compatible protection for N‐terminal cysteine*,†

Abstract: Native chemical ligation has proven to be a powerful method for the synthesis of small proteins and the semisynthesis of larger ones. The essential synthetic intermediates, which are C‐terminal peptide thioesters, cannot survive the repetitive piperidine deprotection steps of N^α‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry. Therefore, peptide scientists who prefer to not use N^α‐t‐butyloxycarbonyl (Boc) chemistry need to adopt more esoteric strategies and tactics in order to integrate ligation approaches with Fmoc chemistry. In the present work, side‐chain and backbone anchoring strategies have been used to prepare the required suitably (partially) protected and/or activated peptide intermediates spanning the length of bovine pancreatic trypsin inhibitor (BPTI). Three separate strategies for managing the critical N‐terminal cysteine residue have been developed: (i) incorporation of N^α‐9‐fluorenylmethoxycarbonyl‐S‐(N‐methyl‐N‐phenylcarbamoyl)sulfenylcysteine [Fmoc‐Cys(Snm)‐OH], allowing creation of an otherwise fully protected resin‐bound intermediate with N‐terminal free Cys; (ii) incorporation of N^α‐9‐fluorenylmethoxycarbonyl‐S‐triphenylmethylcysteine [Fmoc‐Cys(Trt)‐OH], generating a stable Fmoc‐Cys(H)‐peptide upon acidolytic cleavage; and (iii) incorporation of N^α‐t‐butyloxycarbonyl‐S‐fluorenylmethylcysteine [Boc‐Cys(Fm)‐OH], generating a stable H‐Cys(Fm)‐peptide upon cleavage. In separate stages of these strategies, thioesters are established at the C‐termini by selective deprotection and coupling steps carried out while peptides remain bound to the supports. Pilot native chemical ligations were pursued directly on‐resin, as well as in solution after cleavage/purification.     

Surgery for ventricular tachycardia in patients undergoing surgical ventricular restoration: The Karolinska approach

This article presents a review on the efficacy of surgical ventricular restoration and direct surgery for ventricular tachycardia in patients with left ventricular aneurysm or dilated ischemic cardiomyopathy. The procedure includes a non-electrophysiologically guided subtotal endocardiectomy and cryoablation in addition to endoventricular patch plasty of the left ventricle. Coronary artery bypass surgery and mitral valve repair are performed concomitantly as needed. In our experience, this procedure yielded a 90% success rate in terms of freedom from spontaneous ventricular tachycardia, with an early mortality rate of 3.8%. A practical guide to the pre- and postoperative management of these patients is provided. Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users.     

蜂毒和风痛宁穴位注射治疗骨关节炎468例

目的　探索骨关节炎新的有效治疗途径。方法　运用纯中药制剂蜂毒注射液和风痛宁注射液穴位注射治疗本病 ,并与局封治疗作对照比较。结果　治疗组总有效率为 92 .5 2 % ,对照组为 77.0 0 % ,两组比较有显著差异 (P<0 .0 5 ) ,且两组副作用、复发时间均有显著差异 (P<0 .0 5 )。结论　蜂毒和风痛宁穴位注射治疗本病疗效优于局封治疗 ,且能减少副作用 ,延长复发时间。     

鱼腥草注射液佐治下呼吸道感染的疗效观察

目的观察鱼腥草注射液佐治下呼吸道感染的疗效及安全性.方法将76例急性下呼吸道感染患者随机分为治疗组和对照组,两组均予内科常规治疗,治疗组则另予鱼腥草注射液治疗.结果治疗组的总有效率为94.7%,显著优于对照组的73.7%(x2=6.33,P＜0.05),且未见明显副作用.结论鱼腥草注射液佐治急性下呼吸道感染安全、有效,值得推广.     

Peritoneal dialysis patient survival: a comparison between a Swedish and a Korean centre.

BACKGROUND: Dialysis patient mortality remains high, and this high mortality may be due to many factors. In peritoneal dialysis (PD) patients, old age, co-morbid diseases, malnutrition, low residual renal function (RRF) and a high peritoneal transport rate have been shown to influence survival, but the relative importance of these factors may differ between different patient populations. Besides, centre practice patterns may differ between centres and may influence patient survival. In addition, the literature suggests that dialysis patient survival may be better in Asian than in Caucasian patients. METHODS: The influence of centre and patient characteristics on patient survival was investigated in 132 Korean and 106 Swedish incident PD patients, who underwent initial biochemical measurements and assessment of adequacy of dialysis, nutritional status, RRF and peritoneal transport characteristics. RESULTS: At the start of PD, Korean patients had a higher prevalence of diabetes, peritoneal Kt/V(urea), peritoneal creatinine clearance and peritoneal fluid removal, and lower body mass index, RRF and dialysate to plasma creatinine concentration ratio (D/P Cr) compared with Swedish patients. Significantly more patients from Korea were placed on temporary haemodialysis before PD (100 out of 132) when compared with Swedish patients (21 out of 106). During the follow-up, there was a significantly higher rate of transfer to other units in Korea and a significantly higher rate of kidney transplantation in Sweden. On Kaplan-Meier analysis, overall patient survival did not differ and relative risk for death was also not different between the two centres even after adjustment for age, diabetes, cardiovascular disease, RRF and D/P Cr. On Cox proportional hazards multivariate analysis, age, diabetes, RRF and D/P Cr were found to be independent predictors of mortality in the combined cohort of patients. While age, diabetes and D/P Cr were independent predictors of mortality in Korean patients, age and RRF independently predicted mortality in Swedish patients. CONCLUSION: Although there were significant differences in centre and patient characteristics, we were unable to confirm a survival advantage for Korean over Swedish PD patients. The results of this study suggest that the reported difference in survival between Asian and Caucasian dialysis patients may have been due, in part, to differences in centre and patient characteristics rather than to race as such. The genetic influence on patient characteristics remains, however, to be elucidated.     

无名异冲剂促进去卵巢大鼠骨质疏松性骨折愈合的机制研究

为探讨无名异冲剂促进去卵巢 SD大鼠骨质疏松性骨折愈合的机制 ,用 48只 6月龄雄性 SD大鼠建立骨质疏松性骨折模型 ,随机分为模型组、跳骨片组、仙灵骨葆组、无名异冲剂组 ,于灌胃后 2周、4周取材 ,观察 X线片、骨密度、光镜 ,骨痂钙、磷、胶原含量 ,结果显示灌胃第 2周时 ,各组动物各项指标均无显著性差异 ;第4周时 ,无名异冲剂组的骨密度 ,骨痂钙、磷、胶原含量的检测结果与模型组有显著性差异 ( P<0 .0 5 ) ,X线及光镜观察骨痂的生长情况 ,无名异冲剂组也优于模型组 ,说明无名异冲剂能够通过提高骨密度 ,改善骨骼钙、磷、胶原的代谢 ,促进骨折端骨痂的生长 ,达到治疗骨质疏松性骨折的目的。     

市售三厂家18种复方氨基酸注射液的质量评价

目的对市售3厂家(A、B和E)共9批18种复方氨基酸注射液进行质量比较。方法参考国内外同类产品质量标准,从澄明度、透光率、性状、pH值、不溶性微粒、抗氧剂量、细菌内毒素和含量等方面进行比较。结果外观均为无色澄明液体,430nm波长处透光率均大于99%,pH在5.42～6.61间;A、B、E3厂不溶性微粒≥10、≥25μm的粒子数分别为1.41、0.32,0.83、0.21和1.55、0.56个/ml;抗氧剂的量分别为<33、近330和>500mg/L;细菌内毒素检查与含量测定符合中国药典及国家标准要求。结论不同厂家的产品质量确实存在一定的差异。     

不同采血针对新生儿足跟采血成功率的影响

目的：探讨不同采血针在新生儿疾病筛查采血中的采血效果。方法：采用三种采血针分别对2126例（A组）、1786例（B组）、1471例（C组）新生儿进行足跟采血，比较其采血成功率。结果：A、B、C三组之间差异有统计学意义（P〈0．01）。结论：采用7号一次性注射针头采血（C组）可明显提高采血成功率。     

炎琥宁与阿奇霉素联合治疗小儿支原体肺炎

目的:探讨炎琥宁辅助治疗小儿支原体肺炎的疗效.方法:将141例临床确诊的支原体肺炎患儿随机分为两组,治疗组71例,应用阿奇霉素加炎琥宁静点.对照组70例,单纯使用阿奇霉素治疗.结果:治疗组有效率96%,对照组有效率87%,两组统计学差异显著(P＜0.05),治疗组疗效优于对照组.结论:炎琥宁辅助治疗小儿支原体肺炎,临床症状消失快,疗效显著,无明显不良反应,值得推广.     

应用前列腺素E1注射治疗勃起功能障碍8年经验

目的观察前列腺素E1(PGE1)注射治疗勃起功能障碍(ED)的长期疗效、副作用及预后。方法使用PGE1行阴茎海绵体注射,阴茎硬度检查仪(Rigiscan)连续记录1h,并根据观察结果,调查PGE1注射剂量,确定每例患者合适的注射量,掌握注射方法后回家自行注射。共筛选出ED患者410例,随访患者阴茎勃起情况、药量调整和副作用。结果410例ED患者中,心理性139例,静脉性83例,动脉性36例,神经性78例,混合性74例。对治疗满意的患者有256例(62.44%),其中21例(5.1%)在使用PGE15次后停用,并能达到满意的性生活而治愈。293例(71.46%)患者自述注射时有胀痛感。171例(43.17%)因疼痛(105例)、操作不便(25例)、副作用顾虑(37例)和其他原因(4例)而于6个月后放弃治疗。204例(49.76%)患者使用时间已超过1年,24例(5.85%)患者使用时间已超过5年,7例(1.7%)使用已有8年。未发现阴茎异常勃起和阴茎海绵体纤维化。注射损伤阴茎表面血管致瘀斑者有20例。有27例患者失访。结论PGE1是治疗ED的一种安全有效的药物,可以长期使用。其最常见的副作用是阴茎疼痛。Rigiscan能帮助确定PGE1的注射剂量。