Strain differences in distribution of phenylethanolamine N-methyltransferase activity from rat brain and adrenal gland

Phenylethanolamine N-methyltransferase (PNMT) activity was measured in adrenal glands and medulla oblongata from 4 inbred rat strains, Fischer 344, Buffalo, Lewis and Sprague-Dawley rats. Adrenal enzyme activity was markedly different among the strains with the highest in Fischer, followed by Sprague-Dawley, Lewis and Buffalo rats in decreasing order. In medulla oblongata, the PNMT activity of Buffalo rat was the lowest being about one half of that of the other strains. Despite differences in the enzymes activity, immunotitration results indicate that there is no immunochemical difference between adrenal or medulla oblongata PNMT among the strains. Furthermore, the strain differences in the activity are not due to presence of an inactive enzyme, but to the amount of the enzyme. Our preliminary findings by dot blot hybridization, using a 32P-labeled cDNA probe for PNMT suggest that differences in adrenal and medulla oblongata PNMT activity between Fischer and Buffalo rats are partially due to differences in the amount of PNMT mRNA present.     

复方吗啉胍片的非水滴定法

吗啉胍为一抗病毒药物。一般都利用其分子中两个胍基的碱性,采用非水滴定法进行原料或片剂的含量测定。由于片中存在的少量山莨菪碱消耗滴定液,以致干扰测定。但目前往往忽略这项干扰。吗啉胍两个胍基的碱性不同,在水溶液中一分子吗啉胍只与一分子盐酸     

元胡产地醋制法的化学评价

对产地醋制法和传统醋制法的元胡炮制品进行了定性定量分析,其结果证明,两种方法的元胡炮制品主要化学成分相同,而元胡总生物碱及延胡索乙素含量则产地醋制法高于传统醋制法。     

Practical guidance on the initiation,titration, and switching of basal insulins: a narrative review for primary care

Many patients with type 2 diabetes will ultimately require the inclusion of basal insulin in their treatment regimen. Since most people with type 2 diabetes are managed in the community, it is important that primary care providers understand and correctly manage the initiation and titration of basal insulins, and help patients to self-manage insulin injections. Newer, long-acting basal insulins provide greater stability and flexibility than older preparations and improved delivery systems. Basal insulin is usually initiated at a conservative dose of 10 units/day or 0.1–0.2 units/kg/day, then titrated thereafter over several weeks or months, based on patients’ self-measured fasting plasma glucose, to achieve an individualized target (usually 80–130 mg/dL). Through a shared decision-making process, confirmation of appropriate goals and titration methods should be established, including provisions for events that might alter scheduled titration (e.g. travel, dietary change, illness, hospitalization, etc.). Although switching between basal insulins is usually easily accomplished, pharmacokinetic and pharmacodynamic differences between formulations require clinicians to provide explicit guidance to patients. Basal insulin is effective long-term, but overbasalization (continuing to escalate dose without a meaningful reduction in fasting plasma glucose) should be avoided.

Key messages

• Primary care providers often initiate basal insulin for people with type 2 diabetes.
• Basal insulin is recommended to be initiated at 10 units/day or 0.1–0.2 units/kg/day, and doses must be titrated to agreed fasting plasma glucose goals, usually 80–130 mg/dL. A simple rule is to gradually increase the initial dose by 1 unit per day (NPH, insulin detemir, and glargine 100 units/mL) or 2–4 units once or twice per week (NPH, insulin detemir, glargine 100 and 300 units/mL, and degludec) until FPG levels remain consistently within the target range. If warranted, switching between basal insulins can be done using simple regimens.
• The dose of basal insulin should be increased as required up to approximately 0.5–1.0 units/kg/day in some cases. Overbasalization (continuing to escalate dose without a meaningful reduction in fasting plasma glucose) is not recommended; rather re-evaluation of individual therapy, including consideration of more concentrated basal insulin preparations and/or short-acting prandial insulin as well as other glucose-lowering therapies, is suggested.

     

不同治疗方案对急性脑出血合并高血糖患者神经功能预后的影响

目的探讨不同治疗方案对急性脑出血合并高血糖患者神经功能预后的影响。方法共纳入78例我院急性脑出血合并高血糖患者,采用随机数字法平均分为观察组与对照组,观察组给予胰岛素滴定,控制血糖4.4~8.3mmol/L,对照组给予常规治疗,控制血糖4.4~10.0mmol/L。于治疗前、治疗后1d、3d、7d、14d空腹抽取静脉血,检测血清髓鞘碱性蛋白(MBP)、血清胶质纤维酸性蛋白(GFAP)及肿瘤坏死因子(TNF?α)水平,并对其神经功能进行评价。结果观察组血糖水平明显低于对照组,差异有统计学意义(P0.05);但低血糖发生率比较差异无统计学意义(P0.05)。与治疗前相比,治疗后1d、3d2组患者血浆MBP、GFAP、TNF?α水平均明显增高,差异有统计学意义(P0.05);治疗后7d、14d患者血浆MBP、GFAP、TNF?α水平较治疗前明显降低,差异有统计学意义(P0.05),治疗后1d、3d、7d、14d,观察组的血浆MBP、GFAP、TNF?α水平均明显低于对照组,差异有统计学意义(P0.05)。观察组有效率92.3%明显高于对照74.4%,且NIHSS评分亦低于对照组,差异有统计学意义(P0.05)。结论胰岛素滴定治疗可更好控制患者血糖水平,降低MBP、GFAP、TNF?α水平,进而改善患者的神经功能及预后,值得临床推广应用。     

三种方法去除残留消毒剂的效果观察

目的观察三种残余消毒剂去除方法在应用中可能会出现的问题,以求更准确地评价化学消毒剂杀菌效果。方法采用载体定量杀菌试验方法,对化学中和法、稀释法和中和过滤冲洗法等三种方法对抑菌作用较强的胍类消毒剂去除效果进行了评价。结果用5g/L组氨酸、3g/L卵磷脂和30g/L吐温80组成的中和剂,用化学中和法对含50g/L双胍类消毒液中残留作用去除不彻底,各组长菌数不符合中和剂试验要求;但对含5g/L双胍类消毒剂的残留作用可达到有效去除效果。相同的中和剂用中和稀释法,对含50g/L和5g/L两种浓度的胍类消毒剂残留毒性均可达到有效去除效果。用中和过滤冲洗法不能有效去除含量50g/L的胍类消毒液残余作用,但可有效去除含量为5g/L胍类消毒液对试验菌的残留作用。用上述复方中和剂进行杀菌效果评价验证试验,以含50g/L双胍类消毒液对载体上枯草杆菌黑色变种芽孢作用60min,用化学中和法与过滤冲洗去除残余消毒剂,消毒后检不出存活细菌;而用中和稀释法去除残余消毒剂方法消毒后存活菌数为189000cfu/片,平均杀灭率为91.54%。用含5g/L双胍类消毒液对载体上该细菌芽孢作用60min,三种去除残余消毒剂的方法检验出的消毒后存活菌数基本一致,平均杀灭率完全一致。结论三种去除残余消毒剂的方法中,以中和稀释法效果最好,可用于高浓度抑菌作用较强的消毒剂杀菌效果评价。     

Bivalent sequential binding of docetaxel to methyl-β-cyclodextrin

New docetaxel (Dtx) and cyclodextrin (CD) inclusion complexes having improved apparent water solubility (up to 9.98 mg mL⁻¹) were obtained from phase solubility diagrams. γ-CD and SBE-β-CD offered only poor solubility enhancements while considerable increases in apparent solubility were obtained with Me-β-CD (20%, w/w) and HP-β-CD (40%, w/w) (9.98 mg mL⁻¹ and 7.43 mg mL⁻¹, respectively). The complexation mechanism between Dtx and Me-β-CD was investigated by circular dichroism spectrometry, two-dimensional ¹H NMR (NOESY) in D₂O, isothermal titration calorimetry (ITC) and molecular docking calculations. Circular dichroism and NOESY confirmed the existence of non-covalent interactions between Dtx and Me-β-CD and suggested that the tert-butyl group (C₆-C₉) and two aromatic groups (C₂₄-C₂₉ and C₃₀-C₃₅) of Dtx interacted with the Me-β-CD molecules. The combination of ITC results to molecular docking calculations led to the identification of an unconventional sequential binding mechanism between Me-β-CD and Dtx. In this sequential binding, a Me-β-CD molecule first interacted with both tert-butyl and C₃₀-C₃₅ aromatic groups (K₁: 744 M⁻¹). Then a second Me-β-CD molecule interacted with the C₂₄-C₂₉ aromatic group (K₂: 202 M⁻¹). The entropy of the first interaction was positive, whereas a negative value of entropy was found for the second interaction. The opposite behavior observed for these two sites was explained by differences in the hydrophobic contact surface and functional group flexibility.     

基于等温滴定量热技术表征的中药注射剂临床联合用药相容性评价

为建立一种快速评价中药注射剂临床联合用药相容性的方法,采用等温滴定量热法(isothermal titration calorimetry,ITC),考察模式药益气复脉冻干粉针(YQFM)与常用联合用药维生素C注射液(Vc)及5%葡萄糖注射液(5%GS)的相容性,以热力学参数吉布斯自由能(ΔG)、焓变(ΔH)、熵变(ΔS)判断溶合反应类型,以反应活性谱判断反应热量变化,辅以化学特征色谱法进行佐证。结果显示,YQFM与Vc溶合过程中│ΔH│>T│ΔS│,为焓驱动反应,且反应活性谱显示两者溶合放出大量热,即溶合过程中化学反应起主导作用,活性成分发生质变;与5%GS溶合过程│ΔH│相似文献   

Exploring the mechanism of interaction between 5-(ethoxycarbonyl)-6-methyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-one and human serum albumin: Spectroscopic, calorimetric and molecular modeling studies

In this paper, binding interaction of 5-(ethoxycarbonyl)-6-methyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-one (EMMD) with human serum albumin (HSA) under physiological conditions was investigated by using spectroscopy, isothermal titration calorimetry (ITC) and molecular modeling techniques. The results of spectroscopic studies suggested that EMMD have a strong ability to quench the intrinsic fluorescence of HSA through static quenching procedure. ITC investigations indicated that drug-protein complex was stabilized by hydrophobic forces and hydrogen bonds, which was consistent with the results of molecular modeling studies. Competitive experiments indicated the displacement of warfarin by EMMD, which revealed that the binding site of EMMD to HSA was located at subdomain IIA.