灯盏花素分散片的制剂工艺研究

目的 考察处方中组分对灯盏花素分散片制剂的影响。方法 以崩解时限为指标,采用正交设计试验,对灯盏花素分散片处方进行筛选。结果 按优化处方制备的灯盏花素分散片．可在3分钟内完全崩解。结论 优化处方的灯盏花素分散片其体外溶出度明显优于普通片。     

灯盏花素在制剂方面的研究分析

目的：分析研究灯盏花素在制剂方面的进展。方法：通过近些年有关灯盏花素在制剂方面的研究文献及书籍,结合本实验的研究成果进行概述。结果：热熔挤出滚圆制备灯盏花素口服缓释微丸能够大幅提高其生物利用度,工艺简单可行,将成为灯盏花素的一个新制剂。结论：国内对于灯盏花素在制剂方面的研究很多,甚至有扎堆研究现象,导致灯盏花素在制剂方面会有更深入的研究。     

HPLC法测定灯盏花素片中灯盏花乙素的含量

目的:建立灯盏花素片中灯盏花乙素的含量测定方法;方法:采用高效液相色谱法,使用C18柱,流动相为甲醇-水-冰醋酸(30:70:1),检测波长335nm;结果:该制剂中灯盏花乙素在0.2～4.0μg范围内线性良好,平均回收率为100.21%,RSD为1.48%;结论:该方法简便、快速、准确,可用于灯盏花素片的含量测定和质量控制.     

HPLC法测定灯盏花素片中灯盏花乙素的含量

目的建立灯盏花素片中灯盏花乙素的含量测定方法。方法采用高效液相色谱法,使用C18柱,流动相为甲醇-水-冰醋酸(30∶70∶1),检测波长335nm。结果该制剂中灯盏花乙素在0.0624～0.312μg范围内线性良好,平均回收率为99.92%,RSD为0.24%。结论该方法简便、快速、准确,可用于灯盏花素片的含量测定和质量控制。     

灯盏花素新剂型及其质量控制的研究进展

目的探讨灯盏花素新剂型及质量控制的研究进展。方法检索近几年来有关其新剂型及质量控制的研究报道资料。结果灯盏花素新制剂得到了广泛研究,并已有多项专利,主要涉及透皮给药系统、缓控释制剂、脂质体、微粒和纳米粒、包合物、固体分散体、自乳化制剂、分散片等。其制剂的质量控制方法主要有UV、HPLC、HPCE以及HPLC/MS联用技术。结论运用现代药物制剂及其质量控制的新技术和新方法 ,进一步开发生物利用度高,靶向性好的新剂型是极有意义的工作。     

灯盏花素胃漂浮缓释片含量及释放度研究

目的 拟制备灯盏花素胃漂浮缓释片,研究剂型提高其生物利用度.方法 采用HPLC建立灯盏花素胃漂浮缓释片的体外分析方法,考察制剂的体外释放度和漂浮性能.结果 制备的3批灯盏花素胃漂浮缓释片中灯盏乙素的含量合格,RSD％为1.22;在偏碱性条件下,3批灯盏花素胃漂浮缓释片的释放性能基本稳定,均能达到胃漂浮缓释片体外累积释释放的要求.灯盏花素胃漂浮缓释片漂浮性能表明在胃液中持续漂浮达8h以上.结论 该制剂具有提高灯盏乙素利用率的优点,延长药物在胃中的滞留时间,有利于灯盏花素以原形药的形式吸收,为其临床应用提供依据.     

体外条件对不同类型灯盏花素缓控释制剂释放行为的影响

灯盏花素是从灯盏花中提取的黄酮类活性成分,包括灯盏乙素和灯盏甲素.灯盏乙素是其主要活性成分,在临床上被广泛用于治疗脑血管栓塞等症及心血管疾病等[1].随着中药现代化的兴起,将服用次数多、生物利用度低的灯盏花素普通制剂开发成新制剂已成为热点.以渗透泵和凝胶骨架技术为代表的缓控释制剂以其安全、顺应性好等优点发展快速.     

灯盏花素注射液致过敏性休克1例

灯盏花素注射液是从灯盏花中提取的黄酮类有效成分而制成的制剂,主要为黄酮、灯盏花乙素、灯盏花甲素,以灯盏花乙素为主。具有增加血流量、改善微循环、扩张血管、降低血液黏度、降血脂、促纤溶、抗血栓、抗血小板聚集等作用。临床上主要用于冠心病、脑梗死的治疗。本院遇1例灯盏花素注射液致严重不良反应,现报道如下。1临床资料患者,女,46岁,既往有高血压病史两年,不规则服药治疗,血压监测不详。两年前因甲状腺病在绍兴市人民医院手     

银杏制剂等联合用药治疗脑卒中后遗症的临床研究

目的 观察灯盏花素联合银杏制剂治疗脑卒中后遗症的效果.方法 72例脑卒中患者随机分为两组(对照组和治疗组),对照组给予银杏制剂治疗,治疗组采用灯盏花素联合银杏制剂治疗.结果 治疗组的总有效率高于对照组(P<0.05),与对照组比较,治疗组MQ增值明显,差异有统计学意义(P<0.05).治疗期间,患者未发生严重不良反应.结论 银杏制剂和灯盏花素具有协同作用,两者联合治疗脑卒中后遗症疗效显著,安全可靠,可推广应用.     

紫外分光光度法测定灯盏花素粉末注射剂的含量

目的建立紫外分光光度法测定灯盏花素及其制剂中总黄酮含量的方法;方法采用紫外分光光度法,以野黄芩苷为测定指标,与三氯化铝反应,在353nm波长处测定;结果在线性范围内(4.16～20.80μg·mL-1)有良好的线性关系,r=0.9999,平均加样回收率为101.5%;结论所建立的含量测定方法简便可行,结果准确可靠,可用于灯盏花素制剂中总黄酮含量的测定。     

Hepatic effects of 2-butoxyethanol in rodents.

Chronic inhalation of 2-butoxyethanol resulted in an increase in liver hemangiosarcomas and hepatic carcinomas in male mouse liver. No increase in liver neoplasia was observed in similarly exposed male and female rats or female mice. We proposed that the production of liver neoplasia in the male mouse is the result of oxidative damage secondary to the hemolytic deposition of iron in the liver. This occurs selectively in the male mouse and leads either directly or indirectly to liver neoplasia. To address this proposal, male B6C3F1 mice and male F344 rats were treated with 2-butoxyethanol (via daily gavage; five times per week) at doses of 0, 225, 450, and 900 mg/kg/day (mice) and 0, 225, and 450 mg/kg/day (rats) respectively. Following treatment for 7, 14, 28, and 90 days, DNA synthesis, oxidative damage, hematocrit, and iron deposition were measured in the livers. An increase in hemolysis (measured by a decrease in hematocrit and increase in relative spleen weight) was observed in 2-butoxyethanol-treated rats and mice in a dose-dependent manner. An increase in the percentage of iron-stained Kupffer cells was observed following treatment with 450 and 900 mg/kg of 2-butoxyethanol in mice and 225 and 450 mg/kg of 2-butoxyethanol in rats. A biphasic increase in oxidative damage (8-hydroxydeoxyguanosine and malondialdehyde) was seen in mouse liver after 7 and 90 days of treatment with 2-butoxyethanol, whereas no increases were observed in treated rat liver. Vitamin E levels were reduced by 2-butoxyethanol treatment in both mice and rat liver; however, the basal level of vitamin E was approximately 2.5-fold higher in rat than in mouse liver. A similar biphasic induction of DNA synthesis was seen following 2-butoxyethanol treatment in the mouse. In the mouse liver, increased DNA synthesis was observed in hepatocytes at 90 days and in endothelial cells at 7 and 14 days at all doses. No change in DNA synthesis was seen in 2-butoxyethanol-treated rat liver. No apparent differences in apoptosis and mitosis in the liver were observed in mouse and rat liver between 2-butoxyethanol treatment groups and untreated controls. These results suggest that DNA synthesis, possibly from oxidative stress or Kupffer cell activation, occurs selectively in the mouse liver, primarily in endothelial cells (a target of 2-butoxyethanol neoplasia), following exposure to 2-butoxyethanol.     

Evaluation of flushing of a high-selenium backwater channel in the Colorado River

Concern has been raised that selenium contamination may be adversely affecting endangered fish in the upper Colorado River basin. The objective of the study was to determine if operation of a water control structure (opened in December 1996) that allowed the Colorado River to flow through a channel area at Walter Walker State Wildlife Area (WWSWA) would reduce selenium and other inorganic elements in water, sediment, aquatic invertebrates, and forage fish. Endangered Colorado pikeminnow were collected and muscle plug samples taken for selenium analysis. Selenium concentrations in filtered water were 21.0 microg/L in 1995, 23.5 microg/L in 1996, 2.1 microg/L in 1997, and 2.1 microg/L in 1998. Selenium concentrations in sediment cores and sediment traps were 8.5 microg/g in 1995, 8.2 microg/g in 1996, 4.8 microg/g in 1997, and 1.1 microg/g in 1998. Selenium concentrations in aquatic invertebrates were 27.4 microg/g in 1996, 15.5 microg/g in 1997, and 4.9 microg/g in 1998. Selenium concentrations in forage fish were 27.2 microg/g in 1996, 20.2 microg/g in 1997, and 8.6 microg/g in 1998. Selenium concentrations in muscle plugs of Colorado pikeminnow were 9.8 microg/g in 1995, 9.5 microg/g in 1996, 9.0 microg/g in 1997, and 10.3 microg/g in 1998. Although selenium concentrations in water, sediment, aquatic invertebrates, and forage fish decreased substantially after operation of the water control structure, a corresponding change in Colorado pikeminnow did not seem to occur. Selenium concentrations in muscle plugs decreased with increasing fish total length and weight, did not change between repeat sampling in the same year or recapture in subsequent years, and seemed to be most closely associated with the mean monthly river flow for the March-July period.     

Subacute toxicity evaluation in rats exposed to concrete and hwangto building environments

This study examined the potential adverse effects of the subacute exposure of rats to concrete and hwangto building environments. Polycarbonate was used as a comparison. Groups of 10 male rats were exposed to polycarbonate, concrete, or hwangto cages for a 4-week period in summer or winter. During the study period, the clinical signs, mortality, skin temperature, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were examined. The concentration of total volatile organic compounds (VOCs), temperature, and relative humidity in the each cages were also measured. There were no exposure-related effects in any group of the study examined in the summer. The temperature, relative humidity, and the concentration of VOCs in the cages were similar in all groups. However, in the winter study, significant differences in several parameters were detected among the groups. In the concrete group, there was an increase in the clinical signs, a reduction in the body weight gain, food intake, and liver weight, an increase in the lung weight, and an increase in the histopathological alterations in the lung and thymus. Infrared thermal analysis showed that the skin temperature of the rats in the concrete group was lower than that in the polycarbonate group. However, in the hwangto group, there was a decrease in the clinical signs and an increase in the body weight, food intake, and the weights of the heart, lung, spleen, and epididymides. Overall, the 4-week exposure of the rats to the concrete building environment had adverse effects on the clinical signs, skin temperature, body weight, and some organs in the winter but not in the summer. On the other hand, the exposure of hwangto building environment did not have any exposure-related adverse effects on the general health parameters and skin temperature in rats.     

维生素E联合川芎嗪对缺血再灌注幼鼠视网膜损伤后的保护作用研究

目的 观察维生素E联合川芎嗪对幼鼠视网膜缺血再灌注及其外周血氧化相关物质的影响,探讨其对损伤后保护的作用机制.方法 选取清洁级3周龄幼鼠100只,随机分为5组,每组20只.A组为假造模组、B组为模型组、C组为维生素E干预组、D组为川芎嗪干预组、E组为维生素E联合川芎嗪干预组,再灌注损伤后4h处死幼鼠,检测外周血清谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)、超氧化物歧化酶(superioxide dismutase,SOD)、活性氧类物质(reactive oxygen species,ROS)、丙二醛(malondialdehyde,MDA),用Tunel染色法检测视网膜细胞凋亡情况.结果 幼鼠眼球视网膜细胞Tunel指数B组高于其他4组,E组低于C、D组,D组低于C组(P<0.05).Tunel染色阳性集中在细胞核部位,表现为细胞核固缩.GSH-PX、SOD活性B、C、D、E组均低于A组,C、D、E组高于B组,D、E组高于C组,E组高于D组(P<0.05);B、C、D、E组ROS活性和MDA含量均高于A组,C、D、E组均低于B组,且D、E组低于C组,E组低于D组(P<0.05).结论 维生素E联合川芎嗪能通过抑制凋亡与抗氧化对缺血再灌注视网膜起到很好的保护作用,两药联合应用效果更佳.     

A review of poisonous plants that cause reproductive failure and malformations in the ruminants of Brazil

The objective of this review is to provide a report on toxic plants causing reproductive problems in ruminants in Brazil. Aspidosperma pyrifolium causes abortion or stillbirth in goats, as well as most likely in sheep and cattle, in the semiarid regions of Northeastern Brazil. Intoxications by Ateleia glazioveana, Tetrapterys acutifolia and T. multiglandulosa result in abortion and neonatal mortality in cattle and sheep, and the same signs have been experimentally observed in goats. These three plants can also cause cardiac fibrosis and a nervous disease with spongiosis of the central nervous system. Other plants known to cause abortion include Enterolobium contortisiliquum, E. gummiferum, Stryphnodendron coriaceum, S. obovatum and S. fissuratum. These plants can also cause digestive signs and photosensitization. Abortions have been reported in animals intoxicated by nitrates and nitrites as well. Infertility, abortions and the birth of weak offspring have been reported in animals intoxicated by plants containing swainsonine, including Ipomoea spp., Turbina cordata and Sida carpinifolia. Trifolium subterraneum causes estrogenism in cattle. Mimosa tenuiflora and, most likely, M. ophthalmocentra cause malformations and embryonic mortality in goats, sheep and cattle in the semiarid regions of Northeastern Brazil.     

Locomotor and sensorimotor performance deficit in rats following exposure to pyridostigmine bromide, DEET, and permethrin, alone and in combination.

Since their return from Persian Gulf War (PGW), many veterans have complained of symptoms including muscle and joint pain, ataxia, chronic fatigue, headache, and difficulty with concentration. The causes of the symptoms remain unknown. Because these veterans were exposed to a combination of chemicals including pyridostigmine bromide (PB), DEET, and permethrin, we investigated the effects of these agents, alone and in combination, on the sensorimotor behavior and central cholinergic system of rats. Male Sprague-Dawley rats (200-250 gm) were treated with DEET (40 mg/kg, dermal) or permethrin (0.13 mg/kg, dermal), alone and in combination with PB (1.3 mg/kg, oral, last 15 days only), for 45 days. Sensorimotor ability was assessed by a battery of behavioral tests that included beam-walk score, beam-walk time, incline plane performance, and forepaw grip on days 30 and 45 following the treatment. On day 45 the animals were sacrificed, and plasma and CNS cholinesterase, and brain choline acetyl transferase, muscarinic and nicotinic acetylcholine receptors were evaluated. Animals treated with PB, alone or in combination with DEET and permethrin, showed a significant deficit in beam-walk score as well as beam-walk time as compared with controls. Treatment with either DEET or permethrin, alone or in combination with each other, did not have a significant effect on beam-walk score. All chemicals, alone or in combination, resulted in a significant impairment in incline plane testing on days 30 and 45 following treatment. Treatment with PB, DEET, or permethrin alone did not have any inhibitory effect on plasma or brain cholinesterase activities, except that PB alone caused moderate inhibition in midbrain acetylcholinesterase (AChE) activity. Treatment with permethrin alone caused significant increase in cortical and cerebellar AChE activity. A combination of DEET and permethrin or PB and DEET led to significant decrease in AChE activity in brainstem and midbrain and brainstem, respectively. A significant decrease in brainstem AChE activity was observed following combined exposure to PB and permethrin. Coexposure with PB, DEET, and permethrin resulted in significant inhibition in AChE in brainstem and midbrain. No effect was observed on choline acetyl transferase activity in brainstem or cortex, except combined exposure to PB, DEET, and permethrin caused a slight but significant increase in cortical choline acetyltransferase activity. Treatment with PB, DEET, and permethrin alone caused a significant increase in ligand binding for m2 muscarinic acetylcholine receptor (mAChR) in the cortex. Coexposure to PB, DEET, and permethrin did not have any effect over that of PB-induced increase in ligand binding. There was no significant change in ligand binding for nicotinic acetylcholine receptor (nAChR) associated with treatment with the chemical alone; a combination of PB and DEET or coexposure with PB, DEET, and permethrin caused a significant increase in nAChR ligand binding in the cortex. Thus, these results suggest that exposure to physiologically relevant doses of PB, DEET, and permethrin, alone or in combination, leads to neurobehavioral deficits and region-specific alterations in AChE and acetylcholine receptors.     

Tissue-specific regulation of insulin-like growth factors and insulin-like growth factor binding proteins in male diabetic rats in vivo and in vitro

1. Insulin-like growth factors (IGFs) are associated with the development of diabetes mellitus. The liver, kidney and heart have been implicated as important organs in the onset of diabetes mellitus. However, the effect of diabetes on the IGF system in these organs has not been fully described. Thus, we investigated changes in IGF-I, IGF-II and IGF binding proteins (IGFBPs) in male steptozotocin-induced diabetic rats, as well as in a high glucose-induced in vitro model. 2. Serum levels of IGF-I were decreased, but the levels of IGF-II were increased, in diabetic rats compared with controls. The expression of IGFBP-3 in the serum was markedly decreased; in contrast, the expression of IGFBP-1 and -2 was increased in diabetic rats. The expression of IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-4 in the liver of the diabetic group was similar to that in the serum of diabetic rats. 3. In heart tissue of the diabetic group, IGF-I levels were decreased, but IGF-II levels were increased. In addition, the expression of IGFBP-3, IGFBP-1 and IGFBP-2 was decreased in diabetic rats. 4. In the kidney of the diabetic group, IGF-I and IGF-II levels were increased. There was only slight expression of IGFBP-3 in the kidney and this was not altered in diabetic rats. Levels of IGFBP-1 and -2 were markedly increased in the kidney of diabetic rats. 5. Insulin treatment recovered the changes in expression of IGF-I, IGF-II and IGFBPs in the serum, liver, heart and kidney. In the liver, heart and kidney, the expression of the insulin receptor was increased in male diabetic rats. 6. In conclusion, diabetes tissue-specifically alters the IGF system in the liver, heart and kidney in rats; this effect can be recovered by insulin treatment.     

人子宫内膜细胞中 miRNAs 的表达及功能分析

摘要： 目的 探索微小 RNAs （miRNAs, miR） -125b、 miR-30b 和 miR-424 在子宫内膜中的表达及功能。方法 收 集自然周期患者（增殖期和分泌期）和促排卵周期患者（高孕组和非高孕组）的子宫内膜标本, 体外分离培养子宫内 膜上皮细胞和间质细胞, 并用免疫荧光验证。实时定量 PCR 检测 miR-125b、 miR-30b 和 miR-424 的表达。结果 增 殖期, 间质细胞中 miR-125b、 miR-30b 和 miR-424 的表达高于上皮细胞; 分泌期, 间质细胞中 miR-125b 和 miR-424 的表达仍高于上皮细胞, 而 miR-30b 的表达低于上皮细胞。上皮细胞中, 分泌期 miR-125b、 miR-30b 和 miR-424 的 表达显著高于增殖期, 而间质细胞中 3 种 miRNAs 的表达差异无统计学意义。HCG 日高孕组上皮细胞中 miR-125b 的表达高于非高孕组, 间质细胞中 miR-30b 的表达高于非高孕组。miR-125b、 miR-30b 和 miR-424 的靶基因功能 分析发现, 其涉及的生物过程主要有细胞迁移、 运动、 细胞间黏附连接等, 主要富集的信号通路包括胰岛素信号通 路、 VEGF 信号通路、 MAPK 信号通路、 焦点黏附和 Wnt 信号通路。结论 miR-125b、 miR-30b 和 miR-424 在子宫内 膜不同细胞类型、 不同时期和 HCG 日高孕酮患者中的表达存在差异, 可能参与子宫内膜容受性的调节。     

Anti-apomorphine effects of phenothiazine drug metabolites

The potencies in producing muscle relaxation, and in antagonizing apomorphine-induced climbing and hypothermia in mice, were examined for chlorpromazine, levomepromazine and their main metabolites, and for fluphenazine and 7-hydroxy fluphenazine. 3-Hydroxy chlorpromazine was more potent than chlorpromazine in antagonizing apomorphine-induced climbing, while levomepromazine and 3-hydroxy levomepromazine were equipotent in this test. The 3-hydroxy metabolites of chlorpromazine and levomepromazine were more potent than the parent compounds in antagonizing hypothermia, and had significantly weaker muscle relaxant effects than the parent compounds. The 7-hydroxy and N-monodesmethyl metabolites were generally less potent than the parent compounds in antagonizing apomorphine-induced effects. N-Monodesmethyl levomepromazine had a pronounced muscle relaxant effect, like levomepromazine itself. The sulphoxide metabolites of chlorpromazine and levomepromazine were inactive in all tests. Their potencies in these tests indicate that among the metabolites 7-hydroxy chlorpromazine, N-monodesmethyl chlorpromazine and 3-hydroxy levomepromazine, which have all been identified in plasma from patients, may contribute to the antipsychotic effects of the drugs, and furthermore that N-monodesmethyl levomepromazine may contribute to the sedative effects of levomepromazine.     

Subacute oral and dermal toxicity of tert-butyl hydroperoxide in Fischer F344/N rats and B6C3F1 mice

Tert-butyl hydroperoxide (TBHP) is a catalyst frequently used in oxidation and sulfonation reactions in the plastics industry. Since the toxicological evaluation of TBHP remains unknown, the National Toxicology Program (NTP) designed studies to characterize and compare TBHP toxicity by the dermal and oral (gavage) routes in male and female Fischer 344 rats and B6C3F1 mice in 14-day exposures. Rats and mice were administered TBHP at 22, 44, 88, 176 or 352 mg/kg in 0.5% aqueous methylcellulose for the gavage studies. In the dermal studies, mice were administered the same doses as above, while rats were administered four doses (22, 44, 88, 176 mg/kg) in 50% aqueous acetone. Results from the gavage studies revealed treatment-related decreases in survival in male rats and body weights in both male and female rats in the 352 mg/kg group. Clinical signs included post-treatment lethargy, thinness, abnormal breathing, ruffled fur, and/or ataxia which occurred sporadically. The male mice showed a statistically significant decrease in body weight in the 44, 88, 176, and 352 mg/kg groups. The major target organs of toxicity were the forestomach in male and female rats and mice, and the esophagus in male and female rats and in male mice. In addition, there was an increase in the absolute and relative liver weight in female mice with hepatocellular hypertrophy in the top-dose group only. Results from spin trapping experiments revealed the presence of electron paramagnetic resonance signals from radical adducts in the blood and organic extracts of the liver and kidneys of rats treated by gavage with 176 mg/kg TBHP, suggesting the involvement of free- radical generation. The no observed adverse effect level (NOAEL) was considered to be 22 mg/kg in rats and male mice, and 44 mg/kg in female mice. In the dermal studies, there was no effect on survival, body weight, or organ weights in either rats or mice. TBHP administration at the site of application resulted in dermal irritation, hyperkeratosis, hyperplasia, and/or inflammation of the epidermis and inflammation of the dermis at 176 mg/kg and above in male and female rats. Dermal irritation at the site of application was noted in all the mice exposed to 352 mg/kg TBHP. Histopathological lesions in the epidermis and dermis were seen in the 88–352 mg/kg males and in the 176–352 mg/kg females. The NOAEL was found to be 88 mg/kg for male rats and female mice, and 44 mg/kg for female rats and male mice. In conclusion, these studies demonstrate that TBHP is metabolized to free radicals and is a contact irritant affecting skin by the dermal route of exposure, and forestomach and esophagus by oral administration. There was no evidence of systemic absorption by the dermal route of exposure based on lack of pathological findings (Supported by National Institute of Environmental Health Sciences Contract No. N01-ES-65406).