鹌鹑高血尿酸高甘油三酯血症模型塑造

目的和方法:建立一种与人类代谢途径相似的高血尿酸并高甘油三酯血症动物模型。鹌鹑随机分为3组, 除空白对照组外, 模型Ⅰ组以15g·kg^-1·d^-1的酵母食饵喂饲鹌鹑, Ⅱ组以10g·kg^-1·d^-1的酵母食饵喂饲鹌鹑, 动态检测血清尿酸(UA)、甘油三酯(TG)、胆固醇(TC)、尿素氮(BUN)、血糖(GLU)、黄嘌呤氧化酶(XOD)含量。结果:模型Ⅰ组7d后血尿酸水平开始升高, 第2、3、4、5周血UA水平显著高于空白对照组(P＜0.05, P＜0.05, P＜0.05, P＜0.01);第3周血TG水平显著高于空白对照组, 持续至5周, 血BUN含量与空白对照组比差异不显著;GLU及TC可见一过性升高。模型Ⅱ组动物血UA水平亦于第2周升高;TG于第4周显著高于空白对照组, 但持续时间短;血BUN于第2周和第3周显著高于空白组(P＜0.05)。结论:以15g/kg酵母喂饲鹌鹑, 可建立高血尿酸高甘油三酯模型, 以进行尿酸与血脂代谢交互紊乱的药理与病理研究。     

红花水煎剂对家兔离体主动脉血管的舒张作用

目的　观察红花Carthamustinctorius (DFCT)水煎剂对血管肌条的舒张作用及机制。方法　将家兔离体主动脉肌条放置于灌流肌槽中 ,记录其等长收缩。结果　DFCT对血管肌条静息张力无明显影响 ,但 2 0mg/mLDFCT水煎剂与 10 -5mol/L乙酰胆碱相似 ,可使 10 -6mol/L去甲肾上腺素预收缩血管肌条产生明显的舒张作用。去除内皮细胞、10 -4mol/LL NNA或 10 -5mol/L甲烯蓝可减弱DFCT的舒张血管作用 ,但前列腺素合成抑制剂和 β肾上腺素能受体阻断无明显影响。另外 ,4 0mg/mLDFCT水煎剂可明显抑制去内皮血管肌条去甲肾上腺和KCl的量效收缩反应 ,使其PD2 值分别由对照组 6 0 6± 0 0 9和 1 71± 0 33变为 5 0 7± 0 0 8和 1 35± 0 2 0。结论DFCT水煎剂可通过受体操纵Ca2 + 通道和电压依赖性Ca2 + 通道抑制外Ca2 + 内流 ,使血管肌条舒张 ,其作用与内皮释放的NO有关。     

Mixing is required for uniform reconstitution of filter-dried protein antigens in a single-injection vaccine formulation

Ambient temperature filter dried vaccine formulations have been proposed to simultaneously achieve thermostability and offer a ready-to-use immunisation device that combines reconstitution and injection. Vaccine concentration should be uniform at the point of injection, but the uniformity following direct reconstitution of filter-dried vaccines has not been reported. We present here a study of vaccine mixing and release following dissolution of filter-dried model protein and toxoid antigens within a single syringe, filter and needle unit. Release was better for filters made from glass than cellulose. Without additional mixing, uniformity was poor and only 41% of input protein was released from protein filter-dried onto glass fiber. In contrast, adding a simple glass bead and mixing by inversion, 100% release antigen solution was achieved, with uniform concentration at exit from the needle throughout a simulated injection. Adsorption onto alum adjuvant had no detectable effect on vaccine dissolution and mixing. The uniformity and yield of low doses of diphtheria and tetanus toxoid was also improved by mixing, albeit with a lower yield of 60–68%. We conclude that uniformity and mixing should be studied to ensure safety and efficacy of directly reconstituted filter-dried vaccine formulations.     

Preparation of clinical‐scale 177Lu‐Rituximab: Optimization of protocols for conjugation,radiolabeling, and freeze‐dried kit formulation

Rituximab is a monoclonal chimeric antibody, which has been approved by the US Food and Drug Administration for immunotherapy of non–Hodgkin lymphoma. Bexxar and Zevalin are the two other approved radiolabeled antibodies for radioimmunotherapy of non–Hodgkin lymphoma; however, they are of murine origin that reduces their treatment efficacy. So as to circumvent this, efforts have been made to radiolabel Rituximab with various therapeutic radioisotopes. In the present study, an effort has been made to optimize the conjugation (bifunctional chelating agent and antibody) and radiolabeling procedures for the preparation of clinical‐scale ¹⁷⁷Lu‐labeled Rituximab. An attempt was also made to prepare the freeze‐dried Rituximab kit for the easy and convenient clinical translation of the agent. Clinical‐scale ¹⁷⁷Lu‐Rituximab (40 mCi, 1.48 GBq) was prepared with >95% radiochemical purity using the kit. Biological evaluation of ¹⁷⁷Lu‐Rituximab was performed by in vitro cell binding studies in Raji cell lines, which showed satisfactory binding at 4°C and 37°C. Pharmacokinetic behavior of the agent, evaluated by biodistribution studies in normal Swiss mice, revealed high blood and liver uptake at the initial time points, although it exhibited slow and gradual clearance with time. The study indicates that clinical‐scale ¹⁷⁷Lu‐Rituximab could be conveniently formulated using the methodology described in the present article.     

Nutritional composition,microbiological and sensory properties of dried melon: A traditional Turkmen product

Seven different cultivars (Taze vaharman, Gökjek, Arap hatl?, Türkmen vaharman?, Torl? payendeke, Yazk? bi?ek, G?z?l gülab?) of honeydew melons (Cucumis melo L.) from Turkmenistan were processed to a dried traditional product known as ‘kavun kak?’ in order to evaluate the most suitable cultivar for drying process. The chemical composition (dry matter, crude oil, crude protein, crude fibre, energy, ash, water-soluble solids, total sugar, invert sugar, titratable acidity, pH and mineral contents) of the products was determined. The microbiological load (total aerobic bacteria, coliform bacteria and yeasts–moulds) of the samples were also evaluated. There were no significant differences between the odour, taste and texture scores of all the cultivars according to acceptance sensory analysis. The Türkmen Vaharman? and Torl? payendeke samples had the highest colour scores.     

金钗石斛干鲜品的质量比较研究

[目的] 对金钗石斛干鲜品的化学成分及抗氧化活性进行比较研究,了解两者的差别,为金钗石斛干鲜品的区别应用提供依据。[方法] 采用气相色谱法和紫外-可见分光光度法进行成分含量测定比较。采用比色法及试剂盒测定干鲜品对羟自由基的清除作用及抗氧化能力。利用傅利叶变换红外光谱法对干鲜品粉末样品的全息化学特征谱进行比较。[结果] 金钗石斛鲜品的总生物碱和多糖含量及其对羟自由基的清除率和抗氧化能力均显著高于干品。金钗石斛干品与鲜品的红外谱图相似,在1 630 cm^-1、1 506 cm^-1、1 243 cm^-1处,贵州赤水的官渡、长期与红花3个基地的金钗石斛鲜品峰强均大于干品,各个产地金钗石斛鲜品的图谱与多糖对照品图谱的相关系数均大于干品。[结论] 金钗石斛干品与鲜品在化学成分及抗氧化活性方面存在着一定的差异。     

Screening for Gaucher Disease Using Dried Blood Spot Tests: A Japanese Multicenter,Cross-sectional Survey

Objective For patients with Gaucher disease (GD), a rare, inherited lysosomal storage disease, obtaining a definitive diagnosis is currently time-consuming and costly. A simplified screening method to measure the glucocerebrosidase (GBA) activity using dried blood spots (DBS) on filter paper has recently been developed. Using this newly developed screening method, we evaluated real-world GD screening in patients suspected of having GD. Methods This multicenter, cross-sectional, observational study with a diagnostic intervention component evaluated real-world screening in patients suspected of having GD based on their clinical symptoms and a platelet count <120,000/μL. The endpoint was the number of patients with low GBA activity determined using DBS. Results In 994 patients who underwent initial DBS screening, 77 had low GBA activity. The assay was not repeated in 1 patient who was diagnosed as having a high possibility of GD due to clinical symptoms, and a further 21 patients completed the study without undergoing the second assay. Of the remaining 55 patients who had 2 DBS assays performed, 11 had a low GBA activity in both assays. Overall, DBS screening identified 12 (1.2%) patients with a low GBA activity, a proportion consistent with prior screening studies. Conclusion These results suggest that the simplified DBS method was less burdensome to patients, was easily utilized by many physicians, and could be a useful first-tier screening assay for GD prior to initiating burdensome genetic testing.     

Single‐dose administration of clenbuterol is detectable in dried blood spots

Clenbuterol is a β₂‐agonist prescribed for asthmatic patients in some countries. Based on its anabolic and lipolytic effects observed in studies on rodents and in livestock destined for food production, clenbuterol is abused by bodybuilders and athletes seeking leanness. Urinary clenbuterol analysis is part of routine doping analysis. However, the collection of urine samples is time‐consuming and can be intimidating for athletes. Dried blood spot (DBS) appears attractive as an alternative matrix, but the detectability of clenbuterol in humans through DBS has not been investigated. This study evaluated if clenbuterol could be detected in DBS and urine collected from six healthy men after oral intake of 80 μg clenbuterol. The DBS and urine samples were collected at 0, 3, 8, 24, and 72 h post‐ingestion, with additional urine collections on days 7 and 10. Using LC–MS/MS, it was shown that clenbuterol could be detected in all DBS samples for 24 h post‐ingestion and with 50% sensitivity 3 days after ingestion. The DBS method was 100% specific. Evaluation of analyte stability showed that clenbuterol is stable in DBS for at least 365 days at room temperature when using desiccant and avoiding light exposure. In urine, clenbuterol was detectable for at least 7–10 days after ingestion. Urinary clenbuterol concentrations below 5 ng/mL were present in some subjects 24 h after administration. Collectively, these data indicate that DBS are suitable for routine doping control analysis of clenbuterol with a detection window of at least 3 days after oral administration of 80 μg.