Advanced glycation end-products/peptides: a preliminary investigation by LC and LC/MS

An investigation on AGE-peptides, originating by proteolysis of in vitro glycated proteins, was carried out by LC methods with different detection applied to the mixture produced by proteinase K digestion of in vitro glycated human serum albumin (HSA). Classical approaches, like spectroscopic (UV, fluorescence) and mass spectrometric methods (MALDI, LC/ESI/MS), show that the digestion mixture is highly complex. However, there are clearcut differences between the digestion mixtures of glycated and unglycated HSA, in the former case allowing identification of possible glycated peptides belonging to the AGE-peptide class. MS/ MS experiments on selected species seem to be promising as regards structural information.     

老年粘连性肠梗阻诊治分析

目的探讨老年人粘连性肠梗阻的诊治。方法分析223例老年人粘连性肠梗阻患者的诊断和治疗情况。结果腹部X线平片检查后确诊,不完全性肠梗阻98例,完全性肠梗阻125例;手术治疗136例。结论老年人肠梗阻更为复杂,几乎都有腹部手术史,合并症多。往往缺乏典型的临床表现。需腹部X线摄片诊断,治疗方法取决于肠梗阻的性质。难点是发现早期绞窄并及时手术。需进行严密不间断的前后对比观察,一旦肠袢坏死,手术并发症与病死率将明显增高。同时治疗过程中应重视围手术期处理。     

脑囊虫病合并脑积水的影像学诊断与外科手术治疗

目的：探讨脑积水型脑囊虫病的诊断与外科手术治疗效果。方法：对诊断明确的73例脑积水型脑囊虫病患者实施了脑室或脑池囊虫摘除术,术后进行抗脑囊虫病治疗。结果：其中13例脑积水症状改善效果不佳,二次行脑室-腹腔分流术,60例手术均获成功。术后均未出现新的神经损害症状,脑室恢复正常。结论：影像检查是对脑积水型脑囊虫病做出正确诊断的重要依据,积极手术切除脑囊虫,解除梗阻性脑积水术后再进行抗囊虫治疗,必要时再行脑室腹腔分流手术,临床效果明确安全。     

术前放化疗对中晚期直肠癌保肛手术的临床作用价值

目的探讨术前放化疗对中晚期进展期直肠癌保肛手术的临床价值。方法选取郑州人民医院72例直肠癌患者,随机将患者平均分成两组,观察组患者给予术前新辅助放、化疗,对照组患者同期直接手术。随访分析两组患者保肛率及3a生存率。结果近期疗效上,观察组总有效率明显优于对照组（P〈0.05）;远期疗效上,两组3a生存率及术中淋巴结阳性率之间差别均有统计学意义（P〈0.05）;两组保肛率差异也有统计学意义（P〈0.05）。结论术前加用放化疗在提高直肠癌患者保肛率的同时,可以提高患者3a生存率和降低淋巴结转移率,减少手术并发症和局部复发率。但其最终结果和远期疗效有待进一步观察和分析。     

LC/MS/MS与GC/MS法分析鉴定小鼠尿中沙美特罗的代谢产物

目的:鉴定沙美特罗在小鼠尿中的主要代谢产物.方法:ig给药后,收集小鼠尿液,经固相提取,葡萄糖醛酸酶水解,进行LC/MS/MS分析和硅烷化后进行GC/MS分析同时分离鉴定沙美特罗代谢产物.结果和结论:在给药后尿样中发现沙美特罗原型和4种代谢产物M1～M4,其结构推测为19-羟基沙美特罗(M1)、2-羰基沙美特罗(M2)、19-羰基沙美特罗(M3)和19-羟基-8-甲氧基沙美特罗(M4).     

子宫腺肌病与子宫肌瘤的临床对比分析

目的：探讨子宫腺肌病与子宫肌瘤的临床特点及B超、实验室检测的价值,提高对子宫腺肌病术前的诊断率。方法：选择52例子宫腺肌病患者和62例子宫肌瘤患者为研究对象,并对其临床症状、妇科检查、B超结果及血清CA125水平进行比较。结果：两组患者发病年龄和临床症状相近,但子宫腺肌病的痛经症状明显（P〈0.01）;妇科检查子宫腺肌病的子宫常均匀性增大,且一般增大〈12孕周,而宫体压痛明显高于子宫肌瘤（P〈0.01）;两组B超诊断符合率分别为61.5%和93.5%,有统计学差异（P〈0.01）;子宫腺肌病组血清CA125阳性率80.8%,子宫肌瘤组血清CA125阳性率4.8%,有统计学差异（P〈0.01）。结论：综合分析子宫腺肌病与子宫肌瘤的临床表现、妇科检查、B超所见和血清CA125水平有助于提高子宫腺肌病的术前诊断。     

The role of microsphere fabrication methods on the stability and release kinetics of ovalbumin encapsulated in polyanhydride microspheres

The effect of microsphere fabrication methods on the stability and release kinetics of ovalbumin encapsulated in polyanhydride microspheres was investigated. The polyanhydrides used were poly(sebacic anhydride) (poly(SA)) and a 20:80 random copolymer of poly[1,6-bis(p-carboxyphenoxy)hexane] (poly(CPH)) and poly(SA). Microspheres were fabricated using three double emulsion methods (water/oil/water, water/oil/oil and solid/oil/oil) and cryogenic atomization. The encapsulation efficiency was highest for cryogenic atomization and lowest when the w/o/w technique was used. Microspheres fabricated by the s/o/o method had the largest initial burst of released protein. All the methods resulted in zero-order release of the protein after the burst. The release of ovalbumin from poly(SA) and 20:80 (CPH:SA) microspheres lasted ～3 and ～6 weeks, respectively. For all fabrication methods the primary structure of released ovalbumin was conserved as determined by gel electrophoresis. The secondary structure of ovalbumin encapsulated in 20:80 (CPH:SA) w/o/w microspheres was not conserved.     

A Comparison of Abstinence-Oriented and Indefinite Methadone Maintenance Treatment

Advantage was taken of a natural experiment to compare the outcome of abstinence-oriented and indefinite methadone maintenance. Subjects assigned to an abstinence-oriented program were significantly more likely than those assigned to indefinite maintenance to use heroin (OR 1.3) and amphetamines (OR 2.8) during the first 2 years of methadone treatment but less likely to use benzodiazepines (OR 0.7). Subjects discharged from the abstinence-oriented program were significantly more likely to relapse and return to maintenance treatment (RR, first 6 months, 4.2). The abstinence-oriented program was also less able to attract heroin addicts into maintenance treatment.     

Early Versus Late Onset of Alcoholism in the Elderly

The age of onset of alcohol-related problems is a typology that is gaining prominence among clinicians. Findings from epidemiological studies suggest that there are a significant number of older alcoholics who first begin to drink alcohol “abusively” in their later years. While few demographic differences appear between late onset and early onset alcoholics, a number of studies have reported clinical differences be tween these groups that may affect the natural course and treatment outcome of the illness.     

LC/MS/MS法测定辛伐他汀血浆浓度及其在健康人体内的药物动力学研究

目的:建立人体血浆中辛伐他汀的LC/MS/MS测定方法,并研究辛伐他汀片在男性健康志愿者体内的药物动力学行为,评价其生物利用度和生物等效性。方法:采用两制剂双周期自身对照试验设计。18名男性健康志愿者随机交叉服用单剂量辛伐他汀试验片剂和参比片剂20mg,采用液相色谱-串联质谱(LC/MS/MS)分析方法测定血浆辛伐他汀的浓度。采用DAS2.0程序计算药物动力学参数和相对生物利用度,并进行等效性评价。结果:测定单剂量口服20mg辛伐他汀参比片剂和试验片剂的AUC_((0→24))分别为(14.90±5.86)和(14.37±4.94)ng·h·ml~(-1),AUC_((0→∞))分别为(15.62±6.29)和(14.78±5.02 )ng·h·ml~(-1);C_(max)分别为(4.54±2.11)和(4.00±1.34)ng·ml~(-1);T_(max)分别为(1.75±0.79)和(1.39±0.65)h。以AUC_((0→24))与AUC_((0→∞))计算相对生物利用度分别为(108.0±52.7)%和(106.4±52.5)%。结论:该法准确灵敏,测得的数据可靠,统计分析表明两种制剂生物等效。     

国产盐酸舍曲林胶囊和片剂的人体药物动力学及生物等效性

目的研究国产盐酸舍曲林胶囊及片剂的相对生物利用度、药物动力学特征及生物等效性.方法采用随机、开放、3×3拉丁方设计实验,18名男性健康受试者分别单剂量口服含舍曲林50 mg的试验片剂、胶囊及参比制剂.采用HPLC-MS/MS/MS法测定给药后不同时间的血药浓度,计算3者的药物动力学参数及评价其生物等效性.结果 18例健康志愿者口服参比制剂和试验制剂舍曲林胶囊及片剂后,参比制剂中舍曲林的主要药物动力学参数cmax为(10.14±3.43)μg·L-1;tmax为(4.44±1.10)h;AUC0～96为(262.82±100.66)μg·h·L-1;t1/2为(29.19±4.91)h.试验制剂片剂中舍曲林的主要药物动力学参数cmax为(10.16±3.22)μg·L-1;tmax为(4.33±1.85)h;AUC0～96为(269.71±107.47)μg·h·L-1;t1/2为(30.99±6.49)h.试验制剂胶囊中舍曲林的主要药物动力学参数cmax为(10.39±3.59)μg·L-1;tmax为(4.94±1.30)h;AUC0～96为(264.45±112.57)μg·h·L-1;t1/2为(29.68±5.25)h.试验制剂片剂和胶囊分别对参比制剂的相对生物利用度F为(103.4%±18.2%)、(99.8%±13.6%).结论经统计学分析,国产试验制剂胶囊剂和片剂与参比制剂具有生物等效性.     

LC-MS2法鉴别菊花槐米胶囊中掺加的尼群地平成分

目的:建立菊花槐米胶囊中非法掺加尼群地平成分的鉴别方法。方法:采用色谱柱C18(250 mm×2.0 mm);乙腈-水(50∶50)为流动相;流速:0.2 mL.min-1;采用电喷雾离子化(ESI)方式;二级质谱母离子m/z359,碰撞能量20 V。结果:在高效液相色谱、质谱中,样品出现与尼群地平成分一致的色谱峰、质谱峰。结论:本方法简单可行,结果准确可靠,可用于菊花槐米胶囊中掺加尼群地平成分的定性鉴别。     

低剂量甲氨蝶呤给药类风湿性关节炎病人血浆浓度的测定

目的 建立一种快速、灵敏地测定类风湿性关节炎病人血浆中低浓度甲氨蝶呤(MTX)的方法.方法 采用高效液相色谱(HLPC)串联质谱电喷雾检测(LC/MS/MS)法,色谱柱为Ultimate XB-C18柱,流动相为乙腈(1%甲酸):甲酸铵水溶液(20 mmol/L)＝30 ︰ 70,流速为0.2 ml/min,柱温为25℃.样品提取采用液-液萃取的方法,即先用三氟乙酸沉淀蛋白,再用乙酸乙酯提取.提取的样品经电喷雾离子源正离子化后,通过三重四级杆串联质谱仪,采用多反应监测(MRM)对甲氨蝶呤(m/z 455.2→308.2)和内标多索茶碱(m/z 267.1→181.1)进行测定.结果 甲氨蝶呤血药浓度在1～100 ng/ml范围内线性关系良好(r =0.9998),分析方法的最低检测限为0.5 ng/ml,其高、中、低(50、10、2 ng/ml)3 个浓度的平均提取回收率分别为41.2%、49.2%和43.4%, 日内(n = 5)、日间(n = 3)相对标准偏差值(RSD)均<15 %.结论 本方法简单快捷、灵敏、准确、重现性好,可用于低剂量给药的类风湿性关节炎病人的临床血药浓度监测和药动学研究.     

LC/MS/MS法测定癫痫患儿血浆中拉莫三嗪的浓度

目的 建立一种快速、灵敏地测定癫痫患儿血浆中拉莫三嗪(1amotrigine,LTG)的LC/MS/MS方法.方法 采用高效液相色谱串联质谱电喷雾检测(LC/MS/MS)法,色谱柱为Welch Materials XB-C18柱,流动相甲醇-水(95:5,V/V,含5 mmol/L甲酸铵),流速0.3ml/min,柱温...     

液相色谱串联质谱法测定人血清中硝苯地平的浓度

目的建立液相色谱串联质谱法测定人血清中硝苯地平浓度。方法血清样品用甲醇沉淀蛋白,内标为尼群地平,色谱柱为Kromasil C18(4.6mm×150mm,5μm),柱温为30℃,流动相为甲醇-水(90:10,V/V),流速为0.5ml·min-1。质谱采用ESI离子源负离子检测,定量分析的离子对为:m/z345.1/122.0(硝苯地平),m/z359.2/122.0(内标尼群地平)。结果硝苯地平在0.5μg·L-1～50μg·L-1范围内线性关系良好(r=0.9987),批内批间RSD均小于15%,提取回收率为64.06%～77.10%。结论该方法快速,灵敏,准确,可用于硝苯地平的临床药动学研究。     

岩黄连注射液的高效液相色谱质谱联用指纹图谱研究

目的建立岩黄连注射液的指纹图谱。方法色谱部分采用高效液相色谱梯度洗脱法，色谱柱为Kromasil 100-10C₁₈柱(250 mm×4.6 mm ID,5 μm)；流动相为乙腈和水；流速为0.5 mL·min^-1；在254 nm波长下进行分析。质谱部分采用电喷雾离子阱质谱分析，正离子扫描方式。结果通过LC/MS对其中的11种主要成分进行了指认，LC/UV对其中的2种成分进行了定量评价。结论所建指纹图谱能体现岩黄连注射液的特点，相似度评价和方法学考察结果良好，可用于质量控制及定量测定。     

Excitation of striatal neurons by dexamphetamine is not abolished by either chloral hydrate or urethane anaesthesia

In order to understand differences between studies maintaining that dopamine actions are siqnificantly reduced as a result of chloral hydrate anaesthesia or not affected to any appreciable extent, striatal neuronal responses to the indirect dopamine aqonist, dexamphetamine, were examined in rats anaesthetized with either chloral hydrate (400 mg/kg) or urethane (1.5 q/kg). Striatal neuronal activity was markedly depressed by chloral hydrate and urethane. However, striatal neurons still responded to 2.5 mg/kg dexamphetamine with marked excitation. These results indirectly support earlier iontophoretic studies on the excitatory action of dopamine on striatal neurons in chloral hydrate-anaesthetized animals. Furthermore, the ability of dexamphetamine, primarily an indirect dopamine agonist, to excite striatal neurons in these anaesthetized animals suggests that stimulation of both D₁ and D₂ receptors is not abolished by anaesthesia.     

急诊肝切除术治疗肝癌破裂出血

目的探讨急诊肝切除术治疗肝癌自发性破裂的适应证和疗效。方法回顾性分析12例肝癌自发性破裂患者行急诊肝切除术的临床资料。结果急诊肝切除术12例,术后并发症发生率25%（3/12）。术后均行TAE等综合治疗,1、3a生存率分别为75%、41.67%。结论术前综合评估,适当从严掌握手术适应证及完善的围手术期处理是行急诊肝切除术获得成功的重要依据,急诊左半肝肝切除术或左肝外叶切除术治疗肝癌自发性破裂可能获得良好预后。     

Chiari畸形并脊髓空洞的显微外科治疗

目的手术治疗Chiari s畸形并脊髓空洞是迄今惟一有效的方法,目前尚无统一的、标准的外科手术方案,探讨手术治疗Chiari畸形并脊髓空洞最合理有效的手术方式。方法回顾性分析我科85例Chiari畸形并脊髓空洞患者的临床及影像学资料及手术方式与临床疗效。结果 85例患者感觉障碍均得到不同程度的恢复和改善,其中76例症状改善明显,9例病情缓解。结论后颅窝减压、松解并还纳下疝的小脑扁桃体于减压扩大的后颅窝腔,恢复小脑扁桃体正常的解剖位置,改善枕骨大孔区CSF循环通路并枕大池重建是治疗Chiari s畸形并脊髓空洞最佳的外科手术方式。     

抗CCP抗体与RF联合检测的临床诊断意义

目的探讨抗环瓜氨酸肽（CCP）抗体与类风湿因子（RF）联合检测对类风湿性关节炎（RA）诊断的意义。方法用ELISA法和速率散射比浊法检测60例RA患者、45例非RA的风湿病患者和40例健康体检者的血清抗CCP抗体水平和RF水平,比较其敏感性、特异性、阳性预测值和阴性预示值。结果两者联合检测的特异性和阳性预测值均明显高于单独检测（P〈0.05）。结论联合检测两项指标有利于提高RA检测的特异性,对RA的早期诊断有意义。