麻黄中生物碱类有效成分的非水毛细管电泳含量测定

目的 利用非水毛细管电泳(NACE)法对麻黄中各生物碱类有效成分进行含量测定，并比较不同提取方法中各组份含量差异。方法 采用50mmol／L醋酸铵的甲醇溶液，未加入任何其他添加剂，检测波长为210nm。结果 各组份在8min内达基线分离。伪麻黄碱在9．8～147．0μg／mL，去甲基麻黄碱在6．8～102．0μg／mL，麻黄碱在9．4～141．0μg／mL，去甲基伪麻黄碱在4．8～72．0μg／mL，甲基麻黄碱在6．8～102．0μg／mL分别有良好的线性关系。各麻黄碱类回收率在95．0％～100．4％。结论 为麻黄中各生物碱类有效成分的含量测定提供了一种快速、准确和灵敏的测定方法。     

水和非水毛细管电泳-电导检测法分离测定水杨酸类药物

目的建立水和非水毛细管电泳-电导法分离水杨酸类药物。方法用未涂层石英毛细管柱(55 cm×50 μm),以10 mmol·L^-1 Tris-30 mmol·L^-1 H₃BO₃(pH 8.0)为运行缓冲液,分离电压为24 kV,进样时间10 s,电导检测法。结果在非水实验条件下,水杨酸(SA)、乙酰水杨酸(ASA)和磺基水杨酸(SSA)得到很好的分离。SA,ASA和SSA的线性范围分别为0.05～100 mg·L^-1,5.0～250 mg·L^-1,0.08～100 mg·L^-1,r均大于0.995。结论应用于阿斯匹林制剂中水杨酸和乙酰水杨酸含量的测定,结果令人满意。与水介质相比,乙醇介质具有更高的灵敏度和分离效率。     

Accurate prediction of hypoxic-ischaemic encephalopathy at delivery: a cohort study

Objective: Hypoxic-ischaemic encephalopathy (HIE) is a major acute neurologic manifestation of perinatal asphyxia associated with significant mortality and morbidity. The study aimed to develop a simple, accurate method of predicting HIE at delivery. Methods: Between January 2003 and December 2009, all HIE cases were identified from the 38,404 deliveries at a single tertiary centre. Receiver operating curve (ROC) analysis and multivariate logistic regression assessed the ability of clinical and biochemical assessments to predict HIE. Results: Sixty neonates met the HIE criteria: 39 were moderate-severe HIE. Univariate analyses identified clinical neonatal markers (Apgar scores and neonatal resuscitation level) to be better HIE predictors than biochemical markers (umbilical artery pH, base excess and lactate values). Multivariable models using two to four predictors had areas under ROC curves up to 0.98, sensitivities up to 93% and specificities up to 99%. For moderate-severe HIE, the most effective predictor was neonatal resuscitation level and arterial lactate (ROC 0.98, sensitivity 85%, specificity 99%). Conclusion: The combination of umbilical arterial lactate and neonatal resuscitation level provides a rapid and accurate method of predicting moderate-severe HIE that can identify neonates at birth that may benefit from tertiary care and neuroprotective therapies.     

Overcoming the Challenges of Low Drug Solubility in the Intravenous Formulation of Solithromycin

Solithromycin is a fluoro-ketolide (a fourth-generation macrolide) antibiotic that has been undergoing clinical trials for the treatment of community-acquired bacterial pneumonia. In this study, development of the tri-amino acid–buffered solithromycin intravenous (IV) formulation was performed to minimize the occurrence of infusion-associated local adverse events (infusion-site pain or phlebitis) observed in patients who received the tartaric acid–buffered IV formulation with a lower buffered capacity during phase I clinical trials. Development of the tri-amino acids–buffered solithromycin IV formulation was achieved using a dynamic in vitro precipitation model. Computational modeling also supports the superiority of the amino acid-buffered formulation over the tartaric aid–buffered formulation.     

阴离子隙和潜在HCO3^-诊断慢性呼吸衰竭酸碱失衡的临床意义

目的探讨阴离子隙（AG）和潜在HCO3^-判断酸碱失衡类型的应用。方法同步测定动脉血气和血电解质，以酸碱失衡预计代偿公式，结合AG值和潜在HCO3^-对慢性呼吸衰竭患者进行酸碱失衡类型的判断。结果（1）代谢性酸中毒（代酸）31例次，其中高AG代酸22例次，高Cl^-代酸5例次，如不测定AG将有17例次代酸失检；（2）应用AG后，三重性酸碱失衡（TABD）从0增至14例次，在这14例次TABD中，如不应用潜在HCO3^-将有8例失检。结论（1）AG和潜在HCO3^-在提高代酸和TABD诊断率方面发挥了重要的作用，并且提出判断TABD的标准和步骤；（2）因有诸多因素影响AG值，使某些代酸患者AG值不能相应地升高，临床应用时应予注意。     

The Antithrombotic Effects of CI-1028, an Orally Bioavailable Direct Thrombin Inhibitor, in a Canine Model of Venous and Arterial Thrombosis

Direct thrombin inhibitors represent a new class of drug that may offer a therapeutic alternative for the treatment and prevention of thrombembolic conditions, especially on the venous side of the systemic circulation. CI-1028 (PD 172524/LB30057) is a potent, highly selective inhibitor of thrombin that is orally bioavailable. The efficacy of this compound has been demonstrated in animal models in which intra-venous administration was used. The objective of this study was to evaluate the efficacy of CI-1028 after oral administration in a canine electrolytic injury model of venous and arterial thrombosis. CI-1028 was administered via oral gavage, and animals received either saline or 10, 15, 20, or 30mg/kg of drug. Fifteen minutes later, the dogs were anesthetized and a femoral artery and vein were exposed and instrumented to induce electrolytic injury and thrombosis while continuously monitoring blood flow in the vessels. Maximum blood CI-1028 concentrations of 0.88±0.27, 1.8±0.3, 2.2±0.5, and 3.2±0.5g/mL were generally achieved 15 to 30 minutes after administering the compound in the 10-, 15-, 20-, and 30-mg/kg groups, respectively. Administration of CI-1028 increased the time to occlusion (TTO), the principal efficacy end point, in a dose-dependent manner in both arteries and veins. The TTO in the control group (n=8) averaged 66±11 minutes in the arteries and 69±6 minutes in the veins. In dogs treated with 10mg/kg (n=8), the TTO was not significantly different from that of the control group. In the 15-mg/kg group (n=9) TTO averaged 140±27 minutes in the arteries (p=not significant) and 125±15 minutes (p<0.05) in the veins. In the 20-mg/kg group (n=8), TTO was significantly longer than controls in both types of vessels, averaging 168±30 minutes in the arteries (p=0.05) and 155±21 minutes (p<0.05) in the veins. Likewise, at 30mg/kg (n=8) both the arterial (179±17 minutes) and venous (188±15 minutes) TTO was significantly prolonged compared with controls. Surgical blood loss and template bleeding times tended to increase in a dose-dependent manner but a statistically significant elevation was detected for template bleeding time only at the highest dose. Dramatic changes in thrombin time were detected, consistent with the CI-1028 mechanism of action. Virtually no changes were detected in prothrombin time. Maximum activated partial thromboplastin time (aPTT) and activated clotting time changes were detected approximately 30 minutes after dosing, and they were approximately twofold and fivefold baseline values, respectively, at the highest dose. In conclusion, these results demonstrate that CI-1028 provides dose-dependent antithrombotic efficacy after oral administration in a canine model of venous and arterial thrombosis.     

Simultaneous double-isotope autoradiographic measurement of local cerebral glucose metabolic rate and acid-base status in rat brain

We developed a double-isotope autoradiographic method for the simultaneous measurement of the local cerebral metabolic rate for glucose (1CMRG) and index of regional acid-base status (rABI) in single brain slices using [2-¹⁴C]deoxy-D-glucose (DG) and 5,5-dimethyl-[2-¹⁴C]oxazolidine-2,4, dione (DMO). After iv isotope administration, paper chromatography separates plasma DMO from DG activity using a methanol-methylene chloride solvent system. Initial tissue autoradiograms depict regional DMO plus DG and DG metabolite distribution. After 14 days in a well-ventilated hood, 97.5 ±0.5% of all DMO is lost from tissue sections by sublimation, and a second autoradiogram depicts DG plus DG metabolite distribution. Retention of brain lipids does not alter beta-particle self-absorption, avoiding problems associated with isotope extraction with solvents. Autoradiograms are digitized and converted to isotope-content images. The second autoradiogram is used for lCMRG computation. After subtracting the second regional isotope-content value from the first, the DMO content is obtained and used to compute rABI. Application of this method to normal animals yields expected values for lCMRG and rABI. This method is amenable to whole-slice digitization and creation of functional images of lCMRG and ABI followed by pixel-by-pixel correlations of the two variables, making this a potentially valuable tool for the investigation of the relationships between glucose metabolism and brain acid-base balance.     

高渗羟乙基淀粉(200/0.5)氯化钠注射液用于择期颅脑手术麻醉效果探讨

目的 探讨高渗羟乙基淀粉(200/0.5)氯化钠注射液用于择期颅脑手术麻醉对患者血流动力学、电解质酸碱平衡及降低颅内压效果的影响.方法 选取行择期胶质瘤切除手术患者120例,以随机抽样方法分为对照组(60例)和高渗组(60例);分别给予常规羟乙基淀粉和高渗羟乙基淀粉(200/0.5)静脉输注,比较两组患者不同时间点心率(HR),平均动脉压(MAP),中心静脉压(CVP),Na+、K+、Ca2+、pH及颅内压(ICP)等指标水平.结果 两组患者T2、T3及T4时间点HR和CVP指标均较T0时间点明显提高,差异有统计学意义(P＜0.05);两组患者T3和T4时间点MAP指标均较T0时间点显著降低,差异有统计学意义(P＜0.05);而高渗组患者T4时间点HR和MAP指标水平均明显优于对照组,差异有统计学意义(P＜0.05);两组患者T1、T2、T3及T4时间点Na+和K+指标水平与T0时间点比较差异有统计学意义(P＜0.05);两组患者T2、T3及T4时间点ICP水平较T0时间点均显著降低,差异有统计学意义(P＜0.05);高渗组患者T4时间点ICP水平显著低于对照组,差异有统计学意义(P＜0.05).结论 高渗羟乙基淀粉(200/0.5)氯化钠注射液用于行颅脑外科手术治疗患者可有效稳定血流动力学,纠正电解质酸碱平衡平衡紊乱,并抑制颅内压升高.     

多法测量塑料薄膜水蒸气透过量的一致性研究

目的：评价杯式法、电解法和红外法3种方法测量塑料薄膜水蒸气透过量的数据一致性。方法：采用厚度均匀的塑料薄膜,经杯式法、电解法和红外法3种方法测量其水蒸气透过量,等效检验评价测定结果的一致性。结果：杯式法、电解法和红外法测量塑料薄膜的水蒸气透过量分别为7.03、7.02和6.99 g/（m²·day）。结论：3种方法的测量结果等效。这为多种方法测量塑料薄膜水蒸气透过量的实验室数据对比提供了一定的数据基础。