氯化琥珀胆碱注射液的细菌内毒素检查方法的研究

目的建立氯化琥珀胆碱注射液细菌内毒素检查方法。方法采用2005年版中国药典附录细菌内毒素检查法。结果氯化琥珀胆碱注射液可抑制鲎试剂与细菌内毒素的凝胶反应,但通过稀释可消除抑制干扰,将其稀释至0.5mg·ml-1后,用灵敏度为0.25EU·ml-1的鲎试剂进行干扰试验,结果无增强、抑制干扰。结论氯化琥珀胆碱注射液细菌内毒素限值确定为0.5EU·mg-1,可应用鲎试剂进行细菌内毒素法检查。     

高效液相色谱法测定甲氧苄啶注射液的有关物质

目的建立测定甲氧苄啶注射液中有关物质的方法。方法采用高效液相色谱法,用十八烷基硅烷键合硅胶为填充剂,以水-乙腈-三乙胺（799∶200∶1）（用氢氧化钠试液或冰醋酸调节pH值至6.4）为流动相,检测波长：280nm。结果5批样品均检出杂质。结论本法可以用作产品有关物质检查。     

氯化胆碱对尾吊大鼠比目鱼肌肌萎缩对抗效果的观察

目的 探讨氯化胆碱对尾吊大鼠比目鱼肌肌萎缩的影响。方法 按体重配对原则将24只雌性SD大鼠分为对照组（CON）、尾吊组（TS）与尾吊给药组（TS＋Cch），每组8只。尾部悬吊法建立模拟失重模型，1／2尾吊大鼠按150mg／kg的剂量用氯化胆碱灌胃，连续14d。Ca^2＋-ATPase法测定比目鱼肌（SOL）的mATPase活性，常规方法制作石蜡组织切片。结果 1）以氯化胆碱灌胃后，尾吊大鼠SOL中Ⅰ型肌纤维比例明显升高，Ⅱ型肌纤维比例明显降低，P〈0．001；2）以氯化胆碱灌胃后，尾吊大鼠SOL的肌束之间间隙减小，Ⅰ型肌纤维横截面积（CSA）明显升高，P〈0．001，Ⅱ型肌纤维CSA和单根肌纤维的平均CSA亦明显高于尾吊组，P〈0．05；3）以氯化胆碱灌胃后，尾吊大鼠SOL的梭内肌纤维中，一核链纤维的mATPase染色呈阴性，其它各纤维与尾吊组相同，均呈阳性。结论氯化胆碱对模拟失重条件下大鼠SOL慢肌向快肌的转化与模拟失重引起的肌萎缩均有显著的对抗作用。     

氯化琥珀胆碱对大鼠比目鱼肌离体单一肌梭传入放电的影响

目的 探讨不同浓度氯化琥珀胆碱(suxamethonium chloride,Sch)对大鼠比目鱼肌离体单一肌梭传入放电的影响。方法 采用空气隔绝法记录大鼠比目鱼肌离体单一肌梭传入放电,分别给予25 mg/L、50mg/L、75 mg/L、100 mg/L、125 mg/L Sch灌流后,观察大鼠比目鱼肌离体单一肌梭传入放电的变化。结果1)给予25 mg/L Sch灌流后,大鼠比目鱼肌离体单一肌梭传入放电较灌流前无明显变化;2)分别给予50 mg/L、75 mg/L Sch灌流后,肌梭传入放电较灌流前明显增多(P0.01);3)给予100 mg/L Sch灌流后,肌梭传入放电较灌流前无明显变化;4)给予125 mg/L Sch灌流后,肌梭传入放电较灌流前明显减少(P0.05)。结论 一定浓度的氯化琥珀胆碱(50~75 mg/L)可特异性地兴奋肌梭,使大鼠比目鱼肌离体单一肌梭传入放电明显增多;氯化琥珀胆碱浓度过高(≥125mg/L)反而会抑制大鼠比目鱼肌离体单一肌梭的传入放电。     

盐酸纳曲酮质量控制方法的研究

目的：研究盐酸纳曲酮药物质量控制方法，以监测药物纯度。方法：建立了杂质检查的薄层色谱法和高效液相色谱法。结果：两种方法的最小检测限分别为１％和０．２％。对本所合成的４批样品和进口样品（Ｓｉｇｍａ公司）检测均未检出杂质，而粗品检测则均检出明显杂质，两种方法结果相符。结论：上述两种方法均可用于杂质检查，并获得满意结果，薄层色谱法简便易行，高效液相色谱法比薄层色谱法具有较高的灵敏度。     

注射用盐酸头孢替安与三种大输液配伍稳定性研究

目的考察注射用盐酸头孢替安与0.9%氯化钠注射液、5%葡萄糖注射液、5%葡萄糖氯化钠注射液配伍的稳定性。方法采用HPLC法,在室温条件下放置0、1、2、4 h,测定样品有关物质及含量的变化,同时观察pH值变化。结果随着放置时间的延长,各样品的主成分含量均下降,总杂质及单个最大杂质均显著增加,杂质个数也明显增多,室温放置4 h后总杂质含量部分超限;各样品在放置4 h后pH值无明显变化。结论室温条件下,注射用盐酸头孢替安在上述3种溶液中均不稳定,应临床使用前配制。     

少量非去极化肌松剂预防琥珀胆碱所致肌震颤35例观察

琥珀胆碱以其效快 ,作用时间短的特征 ,临床上一直用于快速气管插管术 ,但琥珀肌碱也可引起肌震颤导致胃、眼及颅内压升高 ,血钾增高和术后肌痛等不良反应。本文观察用小剂量的非去极化肌松剂可减少琥珀胆碱的肌震颤作用 ,现报告如下。1　临床资料ＡＳＡⅠ -Ⅱ级择期全身麻醉病人 35例 ,男 2 4例 ,女 11例 ,年龄 33～ 6 5岁 ,手术种类包括胃肠手术 18例 ,胆囊手术 12例 ,脾切除手术 3例 ,其它手术 2例。全部病例术前均无神经肌肉系统及肝肾疾病史 ,术前未用已知能影响肌松作用的药物。2　麻醉方法术前给鲁米那钠 0 1ｇ～ 0 .2ｇ ,阿托品 0 …     

复方茵陈注射液与几种注射液的配伍稳定性考察

目的考察复方茵陈注射液在5%葡萄糖注射液等3种注射液中的配伍稳定性。方法将复方茵陈注射液加入到3种注射液中,采用临床用药浓度和配制方法,在配伍后不同时间,用高效液相色谱法检测配伍液的栀子苷含量,同时检查配伍液的pH值、微粒、澄明度。结果复方茵陈注射液与3种注射液配伍后在室温放置8 h,其pH、澄明度、含量、微粒等指标均无明显异常。结论复方茵陈注射液与5%葡萄糖注射液、10%葡萄糖注射液、氯化钠注射液配伍,8 h内稳定,临床应用时可与上述注射液配伍。     

琥珀胆碱对两种全麻状态下血清钾浓度影响的比较

全麻 硬膜外复合麻醉具有抑制应激反应、减少药物用量、术毕清醒拔管快、便于术后镇痛治疗等优点。琥珀胆碱常用于全麻诱导 ,因升高血清钾浓度而被禁用或慎用[1] 。为此 ,我们对琥珀胆碱在全麻 硬膜外复合麻醉与常规全麻下 ,对血清钾浓度的增幅进行了初步比较 ,结果发现琥珀胆碱引起血清钾浓度的增高幅度以全麻 硬膜外复合麻醉组为显著。1　对象和方法1 1　对象　腹部手术 36例 ,ＡＳＡ分级 1～ 2级。随机分为全麻 硬膜外复合麻醉组 :男 10例 ,女 7例 ;年龄 4 5 4 5± 10 31岁 ,体重 5 7 5 6± 6 82ｋｇ常规全麻组 :男 12例 ,女 7例 ;…     

HPLC-电化学法测定胞磷胆碱钠注射液中游离胆碱含量

目的建立胞磷胆碱钠注射液中游离胆碱含量测定方法。方法采用高效液相色谱电化学检测法,专用色谱柱（ESA ACH-3,250 mm×3 mm ID）和固相胆碱氧化酶反应器（ESA ACH-SPR,3 cm）,M5040分析电极和5300型电化学检测器,柱温：35℃,流速：0.35 ml.min-1。结果游离胆碱在0.12～2.89μg.ml-1范围内呈良好线性关系,r=0.9999,平均回收率为100.0%,RSD为2.7%（n=6）。结论该方法简便可行,重复性好,可用于胞磷胆碱钠注射剂中游离胆碱含量测定。     

百合知母胶囊的质量标准研究

 目的 建立百合知母胶囊的质量标准。方法 采用薄层色谱法（thin layer chromatography,TLC）对百合、知母进行定性鉴别;采用高效液相色谱法（high performance liquid chromatography,HPLC）测定制剂中芒果苷含量。结果 应用薄层色谱法鉴别知母具有专属性,而该法鉴别百合不具有专属性;芒果苷在 0.0674～1.3480 μg范围内呈良好的线性关系,相关系数r=0.9998;检测下限为0.0674 μg,芒果苷的平均回收率为（98.890±0.497）％,RSD=0.50%。结论 本方法操作简便,结果准确,重复性好,可用于该制剂的质量控制。     

Characterization of bone and soft-tissue tumors with in vivo 1H MR spectroscopy: initial results

PURPOSE: To determine if in vivo detection of choline by using hydrogen 1 (1H) magnetic resonance (MR) spectroscopy with dynamic contrast material-enhanced MR imaging can help differentiate between benign and malignant musculoskeletal tumors. MATERIALS AND METHODS: MR imaging was performed in 36 consecutive patients with bone and soft-tissue tumors larger than 1.5 cm in diameter. Examinations were performed at 1.5 T with a surface coil appropriate for the location of the lesions. Single-voxel 1H MR spectroscopy was performed by using a point-resolved spectroscopic sequence with echo times of 40, 135, and 270 msec. The volume of interest within lesions was positioned on the areas of early enhancement (<8 seconds after arterial enhancement) according to the findings of dynamic contrast-enhanced MR imaging with subtraction. The criterion for determining whether choline was present in a lesion was a clearly identifiable peak at 3.2 ppm in at least two of the three spectra acquired at echo times. MR spectroscopic results and histopathologic findings were determined in blinded fashion and compared with kappa statistics. P <.001 was considered to indicate a significant difference. RESULTS: Choline was detected in 18 of 19 patients with malignant tumors and in three of 17 patients with benign lesions. The three benign lesions included one perineurioma, one giant cell tumor, and one abscess. Choline was not detected in 14 patients with benign lesions nor in one patient with a densely ossifying low-grade parosteal osteosarcoma. In vivo 1H MR spectroscopy characterized bone and soft-tissue tumors, resulting in a sensitivity of 95%, specificity of 82%, and accuracy of 89% (P <.001). CONCLUSION: Choline can be reliably detected in large malignant bone and soft-tissue tumors by using a multiecho point-resolved spectroscopic protocol. 1H MR spectroscopy can help differentiate malignant from benign musculoskeletal tumors by revealing the presence or absence of water-soluble choline metabolites.     

Characterization of choline uptake in prostate cancer cells following bicalutamide and docetaxel treatment

Purpose  Choline derivatives labelled with positron emitters are successfully used for PET imaging of prostate cancer patients. Since little is known about uptake mechanisms, the aim of this study was to characterize choline uptake in prostate cancer cells, also following anti-androgen treatment or chemotherapy. Methods  Choline uptake in prostate cancer cells (LNCaP, PC-3) and Michaelis-Menten kinetics were analysed using different concentrations of ³H-choline via liquid scintillation counting. Inhibition of ³H-choline uptake was assayed in the presence of hemicholinium-3 (HC-3), unlabelled choline, guanidine and tetraethylammonium (TEA), an inhibitor of the organic cation transporter (OCT). Changes in choline uptake triggered by bicalutamide and docetaxel were evaluated and choline transporters were detected via Western blotting. Results  Michaelis-Menten kinetics yielded a saturable transport with K_m values of 6.9 and 7.0 μmol/l choline for LNCaP and PC-3 cells, respectively. Treatment of cells with bicalutamide and docetaxel caused an increase in total choline uptake but had no significant effect on K_m values. Uptake of ³H-choline was NaCl dependent and 4.5-fold higher in LNCaP cells than in PC-3 cells. ³H-Choline uptake was reduced by 92–96% using HC-3 and unlabelled choline, by 63–69% using guanidine and by 20% using TEA. The high-affinity choline transporter was detected via Western blotting. Conclusion  Choline uptake in prostate cancer cells is accomplished both by a transporter-mediated and a diffusion-like component. Results of inhibition experiments suggest that uptake is mediated by a selective choline transporter rather than by the OCT. Bicalutamide- and docetaxel-induced changes in total choline uptake could affect PET tumour imaging.     

Radiolabeled choline as a proliferation marker: comparison with radiolabeled acetate

[11C]Choline is a potential tracer to detect tumors, especially brain and prostate cancers. The metabolism of [11C]choline defines the accumulation pattern of [11C]choline in tumors depicted by positron emission tomography. Choline is a precursor of phosphatidylcholine that is a major constituent of membrane lipids. Membrane lipid synthesis as well as DNA synthesis is activated during cell proliferation. We investigated the relation between [14C]choline metabolism and proliferative activity using 10 tumor cell lines and fibroblasts. [14C]Choline uptake was higher in tumor cells than in fibroblasts and was correlated with the proliferative activity, though the sensitivity of [14C]choline uptake to proliferative activity was less than that of [1-14C]acetate. [14C]Phosphocholine produced from [14C]choline by phosphorylation mainly contributed to this accumulation. [11C]Choline can be used for the evaluation of tumor proliferation through estimating choline kinase activity.     

11C]choline uptake in regenerating liver after partial hepatectomy or CCl4-administration

To characterize [methyl-(11)C]choline ([(11)C]choline) as an oncologic PET radiopharmaceutical, [(11)C]choline uptake in regenerating livers after partial hepatectomy as a model of typical proliferating tissue and after CCl(4) insult as that of proliferating tissue with inflammation, was studied in rats. [(11)C]Choline, [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and [2-(14)C]thymidine ([(14)C]TdR) uptake was studied in regenerating rat liver after 70% partial hepatectomy or CCl(4)-administration. [(11)C]Choline uptake in regenerating liver after partial hepatectomy was significantly increased with [(14)C]TdR uptake as a marker of DNA synthesis at 18 hours after surgery. On the other hand, the uptake was not accelerated by CCl(4)-administration, though it significantly increased [(14)C]TdR uptake. There were no differences of [(11)C]choline uptake acceleration following partial hepatectomy among the three parts of the regenerating liver. [(18)F]FDG uptake was accelerated in the regenerating liver on either partial hepatectomy or CCl(4)-administration. The magnitude of the increase in [(18)F]FDG uptake in the regenerating liver induced by partial hepatectomy was greater than that for [(11)C]choline. [(11)C]Choline uptake in the liver was accelerated by partial hepatectomy, but not by CCl(4)-administration. This might be expected given that the differentiation between proliferating tissues such as tumor and inflammatory tissue was possible by [(11)C]choline-PET.     

MR氢质子波谱在乳腺肿块应用中的价值及技术干扰因素分析

目的探讨MR氢质子波谱(1H-MRS)在乳腺肿块中的应用价值及技术干扰因素。方法回顾性分析手术后经病理证实的47个乳腺肿块的1H-MRS特征。其中恶性肿瘤24个,良性肿瘤23个,均于增强扫描前行1H-MRS检测。结果24个恶性病灶中11个于3.24ppm(×10-6)处出现胆碱(Cho)共振峰。23个良性病变中4个于3.24ppm处出现Cho共振峰。以1H-MRS Cho峰鉴别乳腺肿块良恶性,敏感性为45.8%,特异性为82.6%。结论1H-MRS检测到Cho并非乳腺恶性病变的特异表现。不论良性或恶性病变,只要在短期内迅速生长,1H-MRS即可测得Cho。检出率较低的原因主要为技术因素。     

高效液相色谱法测定胞磷胆碱钠注射液中的有关物质

目的 建立胞磷胆碱钠注射液中有关物质的高效液相色谱测定方法.方法 采用C18柱(250 mm ×4.6 mm,5μm),以磷酸盐缓冲液(0.1 mol/L磷酸二氢钾与0.01 mol/L四丁基氢氧化铵等量混合,用磷酸调节pH值至5.2)-甲醇(96:4)为流动相,流速:0.8 ml/min,检测波长:276 nm,柱温...     

In vivo 13C nuclear magnetic resonance investigations of choline metabolism in rabbit brain

The metabolism of choline in rabbit brain was studied by the noninvasive approach of in vivo 13C NMR spectroscopy. 13C-Enriched precursors were introduced into the brain. Surgery of the head skin was avoided through controlled localization of the surface coil. For long-term accumulation studies in brain, repeated subcutaneous injections proved to be advantageous over other forms of application. The resorption kinetics was calculated to be zero order which suggests slow delivery from the subcutaneous depots. Choline metabolism was studied by two approaches: [N-13CH3]choline and S-[13CH3]methionine were administered separately to adult and myelinating rabbits (Days 5 to 32), respectively, over 4 weeks. [N-13CH3]Choline and the 13CH3 group of methionine were incorporated into lecithin and sphingomyelin of brain myelin. In vivo kinetic studies of the turnover of these labeled structures were carried out. Choline and methionine are readily transported through the blood-brain barrier and utilized by the myelinating brain for the biosynthesis of its phospholipids.     

Mapping of brain tumor metabolites with proton MR spectroscopic imaging: clinical relevance.

Brain tumor metabolism was studied with hydrogen-1 magnetic resonance spectroscopy and positron emission tomography with fluorine-18 fluorodeoxyglucose in 50 patients. N-acetylaspartate (NAA) was generally decreased in tumors and radiation necrosis but was somewhat preserved at neoplasm margins. Choline was increased in most solid tumors. Solid high-grade gliomas had higher normalized choline values than did solid low-grade gliomas (P < .02), but the normalized choline value was not a discriminator of tumor grade, since necrotic high-grade lesions had reduced choline values. Serial studies in one case showed an increase in choline as the glioma underwent malignant degeneration. Choline values were lower in chronic radiation necrosis than in solid anaplastic tumors (P < .001). In two cases studied before and after treatment, clinical improvement and a reduction in choline followed therapy. Lactate is more likely to be found in high-grade gliomas, but its presence is not a reliable indicator of malignancy.     

Breast cancer: in vivo proton MR spectroscopy in the characterization of histopathologic subtypes and preliminary observations in axillary node metastases

PURPOSE: To assess the relationship between breast cancer subtypes and choline detection by using in vivo proton magnetic resonance (MR) spectroscopy and to assess the feasibility of proton MR spectroscopy in the study of axillary lymph node metastases. MATERIALS AND METHODS: Breast and lymph node MR spectroscopy of lesions identified at contrast material-enhanced MR imaging was performed in 39 patients with breast cancer. Spectroscopic and histopathologic findings were determined and compared. The sensitivity, specificity, and accuracy of the MR spectroscopic technique in the detection of axillary lymph node metastases were determined. RESULTS: There were four cases of ductal carcinoma in situ (DCIS) and 34 invasive carcinomas, including three with an extensive in situ component. Twenty-six breast lesions were positive for choline at MR spectroscopy; nine, negative; and three, failed cases (ie, determination of positive or negative for choline could not be made). No data were available for one lesion. Four of the nine negative findings were DCIS; three, infiltrating ductal carcinoma (IDC) with an extensive in situ component; and two, IDC. Fourteen axillary lymph nodes were positive for choline; 17, negative; and four, failed cases. No data were available for four nodes. Comparison of the preliminary diagnostic indexes of the MR spectroscopic technique with the ultrasonographically guided fine-needle aspiration biopsy findings in lymph nodes revealed a sensitivity of 82%, specificity of 100%, and accuracy of 90%. CONCLUSION: Choline is consistently detected in IDC. DCIS and IDC with an extensive in situ component are likely to be negative for choline at MR spectroscopy. In vivo proton MR spectroscopy of axillary lymph nodes in patients with breast cancer is feasible and has encouraging preliminary results.