硫酸锌对高脂喂养载脂蛋白E基因敲除小鼠主动脉基质金属蛋白酶-9和CD40表达的影响

目的探讨硫酸锌对高脂喂养载脂蛋白E（ApoE）基因敲除小鼠血脂和氧化低密度脂蛋白（oxLDL）水平,及主动脉中基质金属蛋白酶9（MMP-9）和细胞分化抗原40（CD40）mRNA表达的影响。方法 AopE基因敲除小鼠连续14周喂饲高脂饲料,同时分别给予小鼠浓度为2.5、25 mmol/L硫酸锌水溶液作为低剂量组和高剂量组。测定小鼠血脂和oxLDL水平,并测定主动脉中MMP-9和CD40 mRNA表达水平。结果低剂量组和高剂量组小鼠血清中甘油三酯和oxLDL水平明显低于动脉粥样硬化（AS）模型组（P〈0.01）。低剂量组和高剂量组小鼠主动脉MMP-9 mRNA和CD40 mRNA水平与AS模型组没有差异。结论补充硫酸锌降低了AS模型动物的甘油三酯和oxLDL水平,具有潜在的抗AS作用,但对主动脉MMP-9和CD40 mRNA表达无影响。     

阳离子铝酞菁红区荧光探针测定硫酸软骨素

目的建立以阳离子铝酞菁为红区荧光探针定量测定硫酸软骨素(CS)的新方法。方法在pH5.0的Britton-Robinson(B-R)缓冲溶液中,阳离子铝酞菁与CS发生相互作用形成离子缔合物而导致荧光猝灭。在610 nm波长光的激发下,随着CS的加入,探针的特征发射峰(676 nm)处的荧光强度逐步减弱。结果在最佳条件下,荧光强度差值(ΔIf)与CS浓度(C,μg/mL)在0.2~1.3μg/mL内呈良好的线性关系,工作曲线为ΔIf=406.67C-36.23,r=0.997。建立了溶剂沉淀法成功地进行了样品的前处理,实现了实际样品(滴眼液)的准确测定。结论该法简便、快速、抗金属离子及小分子干扰的能力较强,可用于复杂实际样品中CS的含量测定。     

单甘酯抗血栓形成作用研究

目的观察单甘酯对血栓形成的影响。方法采用动静脉旁路血栓形成方法观察血栓形成并称重。颈总动脉血栓采用电刺激大鼠颈总动脉方法。小鼠肠系膜血管微血栓采用激光照射。肺栓塞采用小鼠尾静脉注射花生四烯酸。测定大鼠血浆纤维蛋白原含量。结果单甘酯25,50 mg.kg-1能够明显减轻动静脉旁路内丝线上血栓重量;单甘酯25,12.5 mg.kg-1能明显延长血管阻塞时间;单甘酯35.7和71.4 mg.kg-1明显延迟小鼠肠系膜血管微血栓出现时间。单甘酯40,80 mg.kg-1能明显降低花生四烯酸所致的小鼠死亡,单甘酯25,50和100 mg.kg-1显著降低大鼠血浆纤维蛋白含量。结论单甘酯具有明显的抗血栓形成作用。     

The effective therapy of cyclosporine A with drug delivery system in experimental colitis

Cyclosporine A (CyA) is a useful immunosuppressive agent for steroid-dependent or steroid-refractory ulcerative colitis. However, side effects have been reported in clinical trials of ulcerative colitis treated with CyA. Biodegradable microspheres (MS) have been investigated as drug delivery system. We evaluated the effect of a drug delivery system with poly(d,l-lactic acid)-MS containing CyA. Colitis was induced in C57BL/6 mice by 3% dextran sulfate sodium (DSS). Mice with DSS-induced colitis were treated with oral administration of CyA or CyA-MS: CyA (0.2?mg/kg/day)-MS; CyA (2?mg/kg/kg)-MS). Serum levels of CyA were significantly less elevated after oral administration of CyA (2?mg/kg/day)-MS compared with CyA (2?mg/kg/day) (CyA (2?mg/kg/day), 44.7 ± 0.8?ng/ml; CyA (2?mg/kg/day)-MS, 7.7 ± 1.3?ng/ml). The body weight at day 10 was significantly recovered in the mice treated with CyA (0.2?mg/kg/day)-MS and CyA (2?mg/kg/day)-MS compared with CyA (0). The histological score and myeloperoxidase activity in the mice treated with CyA-MS was significantly lower than CyA (0). Gene expressions of interleukin-1β (IL-1β), IL-6, and CXCL1 in the mice treated with CyA (0.2?mg/kg/day)-MS and CyA (2?mg/kg/day)-MS were downregulated compared with CyA (0)-MS. CyA-MS might be possible to treat ulcerative colitis effectively by decreasing the total dosage without the elevation of the serum level or the side effects of CyA.     

Innovative pulmonary targeting of terbutaline sulfate-laded novasomes for non-invasive tackling of asthma: statistical optimization and comparative in vitro/in vivo evaluation

Asthma represents a globally serious non-communicable ailment with significant public health outcomes for both pediatrics and adults triggering vast morbidity and fatality in critical cases. The β₂-adrenoceptor agonist, terbutaline sulfate (TBN), is harnessed as a bronchodilator for monitoring asthma noising symptoms. Nevertheless, the hepatic first-pass metabolism correlated with TBN oral administration mitigates its clinical performance. Likewise, the regimens of inhaled TBN dosage forms restrict its exploitation. Consequently, this work is concerned with the assimilation of TBN into a novel non-phospholipid nanovesicular paradigm termed novasomes (NVS) for direct and effective TBN pulmonary targeting. TBN-NVS were tailored based on the thin film hydration method and Box-Behnken design was applied to statistically optimize the formulation variables. Also, the aerodynamic pattern of the optimal TBN-NVS was explored via cascade impaction. Moreover, comparative pharmacokinetic studies were conducted using a rat model. TBN elicited encapsulation efficiency as high as 70%. The optimized TBN-NVS formulation disclosed an average nano-size of 223.89 nm, ζ potential of −31.17 mV and a sustained drug release up to 24 h. Additionally, it manifested snowballed in vitro lung deposition behavior in cascade impactor with a fine particle fraction of 86.44%. In vivo histopathological studies verified safety of intratracheally-administered TBN-NVS. The pharmacokinetic studies divulged 3.88-fold accentuation in TBN bioavailability from the optimum TBN-NVS versus the oral TBN solution. Concisely, the results proposed that NVS are an auspicious nanovector for TBN pulmonary delivery with integral curbing of the disease owing to target specificity.     

可显影固体栓塞剂硫酸钡海藻酸钠微球的研制

目的:研制可显影固体栓塞剂硫酸钡海藻酸钠微球.方法:采用乳化-离子交联法制备微球,正交设计优化工艺,并考察微球的粒径、形态、分布、稳定性、悬浮性、包封率及X线显影性等理化特性.结果:微球平均粒径为(53.08±32.72) μm,分散良好,形态圆整;微球100℃水浴加热2 h、-4℃冰冻24 h、37℃振摇24 h、钴60(10 kGy)照射0.5 h各组的破损率分别为(2.0±1.1)%、(86.0±19.2)%、(39.0±14.7)%和(10.3±3.2)%;0.25%海藻酸钠微球混悬液的沉降体积比为(0.92±0.018);硫酸钡投料量为2.0 g时包封率为(69.2±13.2)%,且显影效果佳.结论:海藻酸钠、壳聚糖可作为硫酸钡微球的包封材料,乳化-离子交联法适用于此微球的制备.     

盐酸利托君与硫酸镁治疗先兆早产的临床分析

目的探讨盐酸利托君治疗先兆早产的临床效果。方法选择2010年7月至2011年12月住院的128例先兆早产的患者,随机分为观察组和对照组,两组均为64例,分别为盐酸利托君治疗组和硫酸镁对照治疗,对两组患者在用药后的起效时间、延长孕周、妊娠结局及不良反应进行分析比较。结果应用盐酸利托君保胎成功率明显高于硫酸镁(P<0.01)。结论盐酸利托君治疗先兆早产其效果好,可用于治疗先兆早产的首选药物。     

两种不同方法治疗小儿输液渗漏的临床观察

目的:探讨硫酸镁溶液加甲磺酸酚妥拉明治疗外周静脉输液渗漏的临床疗效.方法:将我科2004年10月～2005年10月输液发生渗漏的患儿选取60例随机分为治疗组和对照组,治疗组采用硫酸镁溶液加甲磺酸酚妥拉明冷敷,对照组单纯用硫酸镁溶液冷敷.结果:观察1～2 d,治疗组总有效率96.7%,对照组总有效率80.0%,经统计学处理,x2=4.04,P＜0.05,差异有统计学意义.结论:硫酸镁溶液加甲磺酸酚妥拉明冷敷优于单纯用硫酸镁溶液冷敷.     

Isavuconazonium sulfate: a new agent for the treatment of invasive aspergillosis and invasive mucormycosis

Introduction: Invasive fungal infections are serious and life-threatening complications of many of today’s medical enhancements. While we have seen an insurgence of new antifungal therapies on the market since the early 1990s that have contributed significantly to saving lives, there are still important gaps including narrow spectrum of activity, dose-limiting toxicities, or unpredictable pharmacokinetics. Isavuconazonium sulfate hopes to fill several of these gaps.

Areas covered: The in vitro and in vivo pharmacology, pharmacokinetic characteristics, and phase 3 clinical trials for isavuconazole are described with a specific focus on the treatment of invasive aspergillosis and mucormycosis. A literature search was conducted in PubMed as well as FDA and EMA websites, and abstracts from congress proceedings.

Expert Commentary: Isavuconazole’s pharmacokinetic profile, broad-spectrum antifungal activity, and clinical trial data make this new triazole a welcome addition to the armamentarium.     

硫酸氨基葡萄糖氯化钾的制备及对大鼠骨关节炎模型的治疗作用

目的：制备硫酸氨基葡萄糖氯化钾,考察其对大鼠骨关节炎模型的治疗作用。方法：以甲壳素为原料,经盐酸水解得盐酸氨基葡萄糖,将其与硫酸钾置于水溶液中,通过充分的离子交换反应,并加入作为沉淀剂的有机溶剂,制备硫酸氨基葡萄糖氯化钾;考察反应温度、反应溶液中各离子平衡时间、反应原料配比以及沉淀剂的种类、加入量和加入时间等对最终产物的影响,优化制备工艺。建立木瓜蛋白酶诱导的大鼠骨关节炎模型,并灌胃给予硫酸氨基葡萄糖氯化钾,通过血清中丙二醛和一氧化氮含量测定、关节肿胀度观察和关节软骨病理切片检查,考察硫酸氨基葡萄糖氯化钾对模型大鼠骨关节损伤的保护作用。结果：确立优化的硫酸氨基葡萄糖氯化钾制备工艺：反应温度为45~55℃,离子平衡时间为0.5 h,盐酸氨基葡萄糖与硫酸钾的质量配比为22.5：7.15,作为沉淀剂的乙醇加入浓度约为75%及加入时间为3 h。骨关节炎模型大鼠接受硫酸氨基葡萄糖氯化钾给药后,血清中丙二醛和一氧化氮含量显著降低（P〈0.05或P〈0.01）,关节肿胀度明显减轻（P〈0.01）,且病理切片显示,仅有少许关节软骨细胞轻度变性,软骨未见明显坏死,细胞未见明显增生。结论：优化的硫酸氨基葡萄糖氯化钾制备工艺适用于工业化生产;硫酸氨基葡萄糖氯化钾对骨关节炎损伤具有显著保护作用,且效果好于盐酸氨基葡萄糖。