脑脉利颗粒中芍药苷，益母草碱，黄芪甲苷及盐酸水苏碱含量测定

目的：建立脑脉利颗粒中芍药苷,益母草碱,黄芪甲苷及盐酸水苏碱的含量测定方法。方法：采用甲醇、酸水等不同的溶剂提取,并采用高效液相色谱法,液质联用法等灵敏、专属的色谱方法进行含量测定。结果：每10g脑脉利颗粒中含有芍药苷 42.41 mg,益母草碱 1.73mg,黄芪甲苷 0.10 mg,盐酸水苏碱 37.98mg。结论：制剂中其他组分与所测定的各组分分离良好,不干扰测定,可用于脑脉利颗粒中芍药苷,益母草碱,黄芪甲苷及盐酸水苏碱的含量测定。     

Acute and subchronic oral toxicity studies in rats with nanoscale and pigment grade titanium dioxide particles

Data generated using standardized testing protocols for toxicity studies generally provide reproducible and reliable results for establishing safe levels and formulating risk assessments. The findings of three OECD guideline-type oral toxicity studies of different duration in rats are summarized in this publication; each study evaluated different titanium dioxide (TiO₂) particles of varying sizes and surface coatings. Moreover, each study finding demonstrated an absence of any TiO₂ -related hazards. To briefly summarize the findings: 1) In a subchronic 90-day study (OECD TG 408), groups of young adult male and female rats were dosed with rutile-type, surface-coated pigment-grade TiO₂ test particles (d₅₀ = 145 nm − 21% nanoparticles by particle number criteria) by oral gavage for 90 days. The no-adverse-effect level (NOAEL) for both male and female rats in this study was 1000 mg/kg bw/day, the highest dose tested. The NOAEL was determined based on a lack of TiO₂ particle-related adverse effects on any in-life, clinical pathology, or anatomic/microscopic pathology parameters; 2) In a 28-day repeated-dose oral toxicity study (OECD TG 407), groups of young adult male rats were administered daily doses of two rutile-type, uncoated, pigment-grade TiO₂ test particles (d₅₀ = 173 nm by number) by daily oral gavage at a dose of 24,000 mg/kg bw/day. There were no adverse effects measured during or following the end of the exposure period; and the NOAEL was determined to be 24,000 mg/kg bw/day; 3) In an acute oral toxicity study (OECD TG 425), female rats were administered a single oral exposure of surface-treated rutile/anatase nanoscale TiO₂ particles (d₅₀ = 73 nm by number) with doses up to 5000 mg/kg and evaluated over a 14-day post-exposure period. Under the conditions of this study, the oral LD₅₀ for the test substance was >5000 mg/kg bw. In summary, the results from these three toxicity studies – each with different TiO₂ particulate-types, demonstrated an absence of adverse toxicological effects. Apart from reporting the findings of these three studies, this publication also focuses on additional critical issues associated with particle and nanotoxicology studies. First, describing the detailed methodology requirements and rigor upon which the standardized OECD 408 guideline subchronic oral toxicity studies are conducted. Moreover, an attempt is made to reconcile the complex issue of particle size distribution as it relates to measurements of nanoscale and pigment-grade TiO₂ particles. Clearly this has been a confusing issue and often misrepresented in the media and the scientific literature. It is clear that the particle-size distribution for pigment-grade TiO₂, contains a small (“tail”) component of nanoscale particles (i.e., 21% by particle number and <1% by weight in the test material used in the 90-day study). However, this robust particle characterization finding should not be confused with mislabeling the test materials as exclusively in the nanoscale range. Moreover, based upon the findings presented herein, there appears to be no significant oral toxicity impact contributed by the nanoscale component of the TiO₂ Test Material sample in the 90-day study. Finally, it seems reasonable to conclude that the study findings should be considered for read-across purposes to food-grade TiO₂ particles (e.g., E171), as the physicochemical characteristics are quite similar.     

探索中成药治疗儿童咳嗽变异性哮喘的有效性与安全性——小儿咳喘颗粒Ⅱ期临床试验方案设计

目的 初步评价中成药治疗儿童咳嗽变异性哮喘的有效性与安全性,为治疗咳嗽变异性哮喘的中药研发与疾病的临床研究提供参考.方法 采用区组随机、双盲双模拟、剂量探索、阳性药平行对照、多中心临床试验的方法,将144例患儿以1:1:1:1的比例分到高、低剂量,安慰剂以及阳性药组,口服小儿咳喘颗粒试验药及模拟剂,孟鲁司特钠片及其模拟剂.疗程均为4周.以咳嗽严重程度的日平均分为主要疗效指标;把疾病控制情况评估,活动受限、夜间症状、缓解药/急诊需求情况,呼气峰值流速(PEF)日变异率,以及中医证候疗效作为次要疗效指标;以不良事件作为主要安全性指标.结果 建立咳嗽变异性哮喘的评价体系,制定纳入、排除、脱落标准以及主、次要评价指标,并规范了入组时不同慢性咳嗽的鉴别诊断要求.结论 通过小儿咳喘颗粒Ⅱ期临床试验方案设计,对中成药治疗儿童咳嗽变异性哮喘的有效性与安全性进行了有益的探索,在目前条件下该方案具有可操作性.     

喜炎平注射液联合小儿豉翘清热颗粒治疗儿童急性上呼吸道感染的临床研究

目的观察喜炎平注射液联合小儿豉翘清热颗粒治疗儿童急性上呼吸道感染的临床疗效和安全性。方法选取2015年3月—2015年4月汉中市中心医院儿科进行治疗的急性上呼吸道感染患儿120例,随机分为对照组和治疗组,每组患儿各60例。对照组给予小儿豉翘清热颗粒,开水冲服,3次/d,饭后服用,不同年龄组用量不同,6个月~1岁患儿:1~2 g/次;1~3岁患儿:2~3 g/次;4~6岁患儿:3~4 g/次;7~9岁患儿:4~5 g/次。治疗组患者采用喜炎平注射液静脉滴注,1次/d,0.2~0.4 m L/kg,小儿豉翘清热颗粒的用法、用量同对照组。两组患儿均连续治疗5 d。观察两组的临床疗效,同时比较两组治疗前后主要症状、体征消失时间以及血清学指标。结果治疗后治疗组和对照组患儿总有效率分别为96.67%、75.00%,两组总有效率比较差异具有统计学意义(P0.05)。治疗组患儿退热时间、腹泻消失时间、呕吐消失时间、咳嗽消失时间、鼻塞消失时间和咽痛消失时间均显著低于对照组患儿,两组比较差异均具有统计学意义(P0.05)。治疗后两组患儿hs-CRP、TNF-α和IL-6较治疗前显著改善,治疗前后比较差异具有统计学意义(P0.05);治疗后治疗组患儿hs-CRP、TNF-α和IL-6较对照组患儿有显著改善,两组比较差异具有统计学意义(P0.05)。两组患儿在治疗期间均未观察到不良反应。结论喜炎平注射液联合小儿豉翘清热颗粒治疗儿童急性上呼吸道感染临床疗效好,起效快,未发现不良反应,具有一定的临床推广应用价值。     

小儿智力糖浆联合盐酸哌甲酯片治疗儿童注意缺陷多动障碍的疗效观察

目的探讨小儿智力糖浆联合盐酸哌甲酯片治疗儿童注意缺陷多动障碍的临床疗效。方法选择2012年1月—2014年12月重庆市开县人民医院儿科收治儿童注意缺陷多动障碍患者90例,随机分为对照组和治疗组,每组45例。对照组患者口服盐酸哌甲酯片,2片/次,1次/d。治疗组患者在对照组的治疗基础上口服小儿智力糖浆,10 m L/次,2次/d。3周为1个疗程,全部患者均治疗3个疗程。观察两组的临床疗效,同时比较两组治疗前后Conner行为评定量表各因子评分及不良反应情况。结果治疗后,对照组和治疗组总有效率分别为77.78%、88.89%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者冲动多动、多动指数、学习问题、品行问题、焦虑、身心问题评分均较较治疗前显著降低,同组治疗前后差异有统计学意义(P0.05);且治疗组治疗后各评分均显著低于对照组,两组比较差异有统计学意义(P0.05)。两组不良反应发生率比较差异无统计学意义。结论小儿智力糖浆联合盐酸哌甲酯片治疗儿童注意缺陷多动障碍,能够显著提高临床疗效,且无严重不良反应,具有一定的临床推广价值。     

小儿清瘟解热颗粒的解热抗炎镇痛作用

目的:研究小儿清瘟解热颗粒的解热、抗炎及镇痛作用。方法:选取Wistar大鼠,日本大耳白兔,分别采用ih酵母致大鼠发热模型,采用内毒素致家兔发热模型,观察小儿清瘟解热颗粒的解热作用;选取KM小鼠,采用醋酸致小鼠扭体及热板刺激观察小儿清瘟镇痛反应;ICR小鼠,SD大鼠通过小儿清瘟解热颗粒对二甲苯所致耳肿胀,小鼠毛细血管通透性,大鼠后肢足跖炎症性肿胀的影响观察其抗炎作用。结果:小儿清瘟解热颗粒3.92 g·kg-1及15.68 g·kg-1于给药3 h能显著降低家兔肛温差值(P0.05,P0.01),3.78~30.24 g·kg-1于给药4 h能显著降低大鼠肛温(P0.05,P0.01)。小儿清瘟颗粒43.68 g·kg-1显著减少小鼠扭体次数(P0.05),10.92,21.84 g·kg-1于给药2 h能显著提高小鼠痛阈值(P0.05)。小儿清瘟解热颗粒5.46~43.68 g·kg-1连续给药3 d显著减轻二甲苯所致小鼠右耳肿胀度(P0.01),7.56 g·kg-1组于给药1 h显著降低足肿胀度(P0.05),15.12 g·kg-1组于给药0.5,2,4 h显著降低足肿胀度(P0.05,P0.01),30.24 g·kg-1组于给药0.5~4 h显著降低足肿胀度(P0.05,P0.01),小儿清瘟解热颗粒43.68 g·kg-1组腹腔冲洗液吸光度值显著低于模型组(P0.05)。结论:小儿清瘟解热颗粒具有解热、抗炎及镇痛作用。     

异种脱细胞真皮基质覆盖自体微粒皮治疗大面积深度烧伤疗效分析

目的：分析研究异种脱细胞真皮基质覆盖自体微粒皮治疗大面积深度烧伤的临床疗效。方法随机选取该院在2013年2月-2015年1月间接诊的30例大面积深度烧伤患者作为研究对象,所有患者早期均进行切(削)痂术治疗,并采用异种脱细胞真皮基质覆盖自体微粒皮进行创面治疗,观察患者脱细胞真皮基质的变化情况以及患者创面的修复情况。结果术后所有患者异种脱细胞真皮基质敷料与创面均贴敷良好且未有明显溶解、脱落现象出现。30例患者均在3~4周内脱细胞猪皮逐渐脱水干燥,治疗2个月后,创面完全愈合、无水泡以及溃疡情况出现,且愈合质量较高、移植皮肤弹性良好。结论异种脱细胞真皮基质覆盖自体微粒皮治疗大面积深度烧伤的临床疗效较好,具有临床推广应用价值。     

红细胞膜免疫磁珠检测成分血中抗A/抗B的研究

目的比较应用红细胞膜免疫磁珠法及传统方法进行成分血中抗A/抗B效价检测之间的相关性。建立应用红细胞膜免疫磁珠检测血浆标本中高效价抗体的方法。方法采用新鲜细胞试管法、微柱凝胶法及红细胞膜免疫磁珠法进行血浆样本抗体效价检测。将试管法检测效价≥128的样本10倍、15倍、20倍稀释后,用红细胞膜免疫磁珠检测,测定其凝集强度。结果微柱凝胶法最敏感,其次为试管法,红细胞膜免疫磁珠法低于试管法1个滴度。将试管法检测效价≥128的待检样本15倍稀释后,用红细胞膜免疫磁珠检测,其凝集强度≥2+。结论红细胞膜免疫磁珠可做为标准红细胞抗原应用于抗体效价检测,将样本进行15倍稀释,若凝集强度≥2+,则可视其带有高效价抗体。     

Encapsulation of aluminium hydroxide fillers with polymethyl-methacrylate

A process was developed for the microencapsulation of inorganic filler particles with poly-methyl-methacrylate, to increase the interaction between the hydrophilic filler particles and a polymer matrix. The filler utilised was aluminium hydroxide with an average diameter of 1.9 µm and a specific surface area of 5 m2/g. The process comprised a surface modification, in which a monolayer of isopropoxy titanium isostearate was chemically bound to the surface to render it hydrophobic and to ensure a chemical bond between the filler and the organic phase. Then, an encapsulation reaction was carried out by means of an emulsion-like polymerization process at monomer starved conditions. The modified particles were stabilized in water with sodium-dodecyl-sulphate. A redox system consisting of cumene-hydroperoxide in combination with sodium-formaldehyde-sulphoxylate and iron(II) salt was applied for the initiation of the polymerization. Besides surface polymer, free polymer particles were also formed. The parameters which varied were the filler concentration, the concentration of the initiator components and the surfactant concentration. At optimum conditions, ~50% of the added monomer polymerized at the modified filler surface, thus forming encapsulated filler particles. SEM together with TGA analysis indicated that a smooth polymer layer had been formed on the filler surface. At high filler loading, however, coagulation occurred.     

Silica nanoparticles induce cytokine responses in lung epithelial cells through activation of a p38/TACE/TGF-α/EGFR-pathway and NF-κΒ signalling

Amorphous silica nanoparticles (SiNPs) have previously been shown to induce marked cytokine (interleukin-6; IL-6 and interleukin-8; CXCL8/IL-8) responses independently of particle uptake in human bronchial epithelial BEAS-2B cells. In this study the involvement of the mitogen-activated protein kinases (MAP-kinases), nuclear factor-kappa Β (NF-κΒ) and in particular tumour necrosis factor-α converting enzyme (TACE) and—epidermal growth factor receptor (EGFR) signalling pathways were examined in triggering of IL-6 and CXCL8 release after exposure to a 50 nm silica nanoparticle (Si50). Exposure to Si50 increased phosphorylation of NF-κΒ p65 and MAP-kinases p38 and JUN-N-terminal protein kinase pathways (JNK), but not extracellular signal regulated kinases (ERK). Inhibition of NF-κΒ and p38 reduced the cytokine responses to Si50, whereas neither JNK- nor ERK-inhibition exerted any significant effect on the responses to Si50. Increases in membrane-bound transforming growth factor-α (TGF-α) release and EGFR phosphorylation were also observed after Si50 exposure, and pre-treatment with inhibitors of these pathways reduced the release of IL-6 and CXCL8, but did not affect the Si50-induced phosphorylation of p38 and p65. In contrast, p38-inhibition partially reduced Si50-induced TGF-α release, while the p65-inhibition was without effect. Overall, our results indicate that Si50-induced IL-6 and CXCL8 responses in BEAS-2B cells were regulated through combined activation of several pathways, including NF-κΒ and p38/TACE/TGF-α/EGFR signalling. The study identifies critical, initial events in the triggering of pro-inflammatory responses by nanoparticles.