盐酸胍诱导的α淀粉酶去折叠与再折叠

利用蛋白质内源荧光和酶活性两种信号以及荧光偏振,HPLC和停流等方法研究了盐酸胍诱导的α淀粉酶去折叠与重折叠的平衡转变和动力学。实验结果表明α淀粉酶去折叠与重折叠是两个不同的过程;变性与复性过程中可能伴有聚集体生成;去折叠与重折叠均为双相过程,重折叠大约始于2秒之后。     

Transferrin Modifications and Lipid Peroxidation: Implications in Diabetes Mellitus

Free iron is capable of stimulating the production of free radicals which cause oxidative damage such as lipid peroxidation. One of the most important mechanisms of antioxidant defense is thus the sequestration of iron in a redox-inactive form by transferrin. In diabetes mellitus, increased oxidative stress and lipid peroxidation contribute to chronic complications but it is not known if this is related to abnormalities in transferrin function. In this study we investigated the role of transferrin concentration and glycation. The antioxidant capacity of apotransferrin to inhibit lipid peroxidation by iron-binding decreased in a concentration-dependent manner from 89% at <formula>≥2 mg/ml</formula> to 42% at 0.5 mg/ml. Pre-incubation of apotransferrin with glucose for 14 days resulted in a concentration-dependent increase of glycation: 1, 5 and 13 μmol fructosamine/g transferrin at 0, 5.6 and 33.3 mmol/l glucose respectively, p<0.001. This was accompanied by a decrease in the iron-binding antioxidant capacity of apotransferrin. In contrast, transferrin glycation by up to 33.3 mmol/l glucose did not affect chemiluminescence-quenching antioxidant capacity, which is iron-independent. Colorimetric evaluation of total iron binding capacity in the presence of an excess of iron (iron/transferrin molar ratio=2.4) also decreased from 0.726 to 0.696 and 0.585 mg/g transferrin after 0, 5.6 and 33.3 mmol/l glucose, respectively, p<0.01. In conclusion, these results suggest that lower transferrin concentration and its glycation can, by enhancing the pro-oxidant effects of iron, contribute to the increased lipid peroxidation observed in diabetes.     

Crystal structure of the human collagen XV trimerization domain: A potent trimerizing unit common to multiplexin collagens

Correct folding of the collagen triple helix requires a self-association step which selects and binds α-chains into trimers. Here we report the crystal structure of the trimerization domain of human type XV collagen. The trimerization domain of type XV collagen contains three monomers each composed of four β-sheets and an α-helix. The hydrophobic core of the trimer is devoid of solvent molecules and is shaped by β-sheet planes from each monomer. The trimerization domain is extremely stable and forms at picomolar concentrations. It is found that the trimerization domain of type XV collagen is structurally similar to that of type XVIII, despite only 32% sequence identity. High structural conservation indicates that the multiplexin trimerization domain represents a three dimensional fold that allows for sequence variability while retaining structural integrity necessary for tight and efficient trimerization.     

盐酸右美托咪定联合瑞芬太尼在骨科手术中的镇静效果及对患者血流动力学和呼吸功能的影响

目的:探讨盐酸右美托咪定联合瑞芬太尼在骨科手术中的镇静效果及对患者血流动力学和呼吸功能的影响。方法:选择2016年3月至2017年5月在我院186例行骨科手术的患者,根据数表法随机分为对照组(93例)和观察组(93例),对照组采用丙泊酚联合瑞芬太尼进行麻醉,观察组采用盐酸右美托咪定联合瑞芬太尼进行麻醉,比较两组用药前(T_1)、联合用药后10 min(T_2)、联合用药后20 min(T_3)、联合用药后30 min(T_4)和患者清醒后(T_5)等时间点的镇静效果以及血流动力学和呼吸功能指标变化,并比较两组不良反应发生率。结果:T_3、T_4时间点两组警觉/镇静(OAA/S)评分低于组内其他时间点,且观察组OAA/S评分低于对照组(P0.05)。两组T_1、T_5时间点呼吸频率(RR)、血氧饱和度(SpO_2)比较差异无统计学意义(P0.05);在T_2、T_3、T_4时间点观察组RR、SpO_2高于对照组(P0.05);T_3、T_4时间点两组的RR水平均低于组内其他时间点(P0.05)。两组各时间点平均动脉压(MAP)、心率(HR)水平比较差异均无统计学意义(P0.05)。观察组呼吸抑制、呼吸道梗塞和恶心呕吐的发生率低于对照组(P0.05)。结论:盐酸右美托咪定联合瑞芬太尼在骨科手术中镇静效果良好,对患者血流动力学的影响较小,呼吸抑制程度轻,安全性好。     

盐酸右旋美托咪定对脑膜瘤切除术患者围拔管期应激反应的影响

目的：观察不同剂量的盐酸右旋美托咪定对脑膜瘤切除术患者全麻围拔管期应激反应的影响。方法：60 例ASAI～Ⅱ级,年 龄25-65 岁脑膜瘤切除术患者,随机分为四组,NS、D1、D2 和D3 组,NS 组:静脉泵入等量的生理盐水,D1、D2 和D3组静脉泵注 负荷量均为0.6 滋g/kg 的盐酸右旋美托咪定,各组泵注时间均为10 分钟,输注结束后随之给予维持量,D1组：盐酸右旋美托咪定 维持量0.2 滋g·kg-1·hr-1;D2 组：盐酸右旋美托咪定维持量0.4 滋g·kg-1·hr-1;D3组：盐酸右旋美托咪定维持量0.6 滋g·kg-1·hr-1。观察 并记录拔管时的耐管评分、呛咳程度、警觉/ 镇静评分(OAA/S）、拔管时间及拔管即刻和拔管后3 min 的平均动脉压(MAP)、心率 (HR)及恶心、寒战等不良反应。结果：D3 组患者耐管评分高于D1 组、D2 组和NS 组,呛咳程度轻于D1 组、D2 组和NS 组（P<0. 05）;D2、D3 组患者拔管即刻和拔管后3 min 的MDP、HR 均明显低于D1 组（P<0.05）;D1、D2 和D3 组不良反应少于NS 组;四组 拔管时间无明显差异。结论：盐酸右旋美托咪定降低脑膜瘤切除术患者全麻围拔管期的应激反应,增强患者对气管导管的耐受 性。     

盐酸氨基葡萄糖片联合玻璃酸钠治疗颞下颌关节骨关节炎的疗效观察

目的:研究盐酸氨基葡萄糖片联合玻璃酸钠治疗颞下颌关节骨关节炎(TMJOA)的临床疗效,为临床治疗提供依据。方法:选取2012年11月到2015年11月我院收治的TMJOA患者60例,按照随机数字表法将患者分为研究组和对照组,每组30例,两组均给予玻璃酸钠关节腔注射,研究组在此基础上给予盐酸氨基葡萄糖片治疗,应用视觉模拟评分法(VAS)评价关节疼痛情况,比较两组临床疗效和不良反应,比较治疗前后两组最大张口度、张口VAS评分和张口偏斜。结果:研究组总有效率为83.33%(25/30),显著高于对照组的56.67%(17/30),比较差异具有统计学意义(P0.05);治疗后两组张口VAS评分和张口偏斜显著降低,最大张口度显著增高,且研究组显著优于对照组,比较差异具有统计学意义(P0.05);两组不良反应发生率比较差异无统计学意义(P0.05)。结论:盐酸氨基葡萄糖片联合玻璃酸钠治疗TMJOA具有较好的临床疗效,能有效改善患者关节功能。     

Simultaneous determination of enantiomers of structurally related anticholinergic analogs in human serum by liquid chromatography–electrospray ionization mass spectrometry with on-line sample cleanup

Trihexyphenidyl, biperiden and procyclidine are anticholinergic drugs produced as racemates for the treatment of Parkinson’s disease. This paper describes a simple and sensitive LC–MS method for the simultaneous determination of these compounds in human serum. An on-line sample clean-up procedure was used, where serum samples were directly injected into a “restricted-access media” pre-column. After the exclusion of the serum proteins, the drug molecules were eluted to a β-cyclodextrin analytical column for chiral separation. The quantitation was done by electrospray ionization MS using diphenidol as an internal standard. The method developed has limits of detection of 1 ng/ml, at least two-orders-of-magnitude linear dynamic ranges (r>0.999), and RSDs of less than 10%. The system can be completely automated for increased sample throughput and unattended analyses.     

低温法配制盐酸川芎嗪氯化钠注射液

目的:探讨盐酸川芎嗪氯化钠注射液的配制条件。方法:改造现有蒸汽夹层锅,将注射用水快速降温到40℃～50℃,用此低温水配制盐酸川芎嗪氯化钠注射液,并与高温法配制的注射液进行对比研究。结果:高温配制法配制的注射液盐酸川芎嗪含量均<90.0%,达不到质量标准,而低温法配制的注射液盐酸川芎嗪含量均>99.0%,完全符合质量要求;两种方法配制的注射液氯化钠含量符合质量要求。高温法配制的注射液中有关物质含量较高,且20040506批号样品含量超标,而低温法配制的注射液中,有关物质含量均符合质量要求。低温法制备的注射液室温条件下放置半年,有效成分含量均>99.0%,有关物质含量均<1.0%。结论:在低温条件下(40℃～50℃)配制盐酸川芎嗪氯化钠注射液,盐酸川芎嗪及有关物质含量符合要求;通过改造现有设备快速大量制备低温注射用水,以实现制剂的低温配制。     

穴位敷贴法联合盐酸羟考酮缓释片对中重度癌性疼痛患者负性情绪及生活质量的影响

目的:探讨穴位敷贴法联合盐酸羟考酮缓释片对中重度癌性疼痛患者负性情绪及生活质量的影响。方法:选取2015年6月-2017年10月期间海南省人民医院收治的恶性肿瘤患者90例为研究对象。根据随机数字表法将患者分为对照组(n=45)与研究组(n=45),对照组患者给予盐酸羟考酮缓释片治疗,研究组患者在此基础上联合使用穴位敷贴法治疗。观察两组患者治疗后疼痛缓解情况及不良反应发生情况,比较两组患者治疗前后抑郁自评量表(SDS)评分、焦虑自评量表(SAS)评分以及生活质量情况。结果:研究组患者疼痛缓解率为66.67%(30/45),高于对照组的48.89%(22/45)(P0.05)。两组患者治疗后SDS评分、SAS评分均较治疗前降低,且研究组低于对照组(P0.05)。两组患者治疗后睡眠、饮食、日常生活以及情绪等评分均较治疗前降低,且研究组低于对照组(P0.05)。研究组患者恶心、头晕、排尿困难、便秘等发生率均低于对照组,差异有统计学意义(P0.05),而研究组皮肤刺激发生率与对照组相比差异无统计学意义(P0.05)。结论:穴位敷贴法联合盐酸羟考酮缓释片治疗可减轻中重度癌性疼痛患者疼痛程度,改善其负性情绪及生活质量,且不良反应较少。     

盐酸胍处理大麦类囊体膜对金属阳离子调节激发能分配的影响

以大麦（ＨｏｒｄｅｕｍＶｕｌｇａｒｅＬ）叶片为实验材料,研究盐酸胍处理大麦类囊体膜对金属阳离子调节激发能分配的影响。结果表明：当未用盐酸胍处理时,Ｍｇ２＋对类囊体膜的Ｆ６８６／Ｆ７３６比值有显著的刺激作用,而用不同浓度盐酸胍处理类囊体膜,则明显阻滞Ｍｇ２＋调节激发能向ＰＳＩＩ分配,表明盐酸胍处理可能损伤类囊膜上ＬＨＣ—ＩＩ与Ｍｇ２＋调节作用有关的蛋白质,从而导致Ｍｇ２＋调节效应降低．用ＳＤＳ—ＰＡＧＥ方法研究盐酸胍处理后的类囊体膜色素蛋白复合物的组成变化,结果表明盐酸胍处理导致ＭＩＣ—ＩＩ中ＭＩＣＰ１和ＬＨＣＰ２组分消失,这说明盐酸胍处理阻滞Ｍｇ２＋调节效应可能与ＬＪＩＣ—ＩＩ上的ＬＨＣＰ１,ＬＨＣＰ２受损有关。