β3-肾上腺素受体激动剂的研究进展

摘要β     

Effects of cannabidiol and of diphenylhydantoin on the hippocampus and on learning

Cannabidiol (3.5 mg/kg, i.p.) depressed hippocampal facilitation and posttetanic potentiation of evoked responses in rats, such, as had been reported before for diphenylhydantoin. Both diphenylhydantoin (80 mg/kg, i.p.) and cannabidiol blocked the increase of hippocampal RNA concentration caused by afferent stimulation, and depressed the acquisition of a conditioned avoidance response in rats. Neither drug affected the retention of such response when given by posttrial injection, nor the spontaneous locomotor activity of mice. The effects of both agents may be explained by the interference they have been previously shown to produce with the release of K⁺ from the hippocampus during stimulation. In fact, hippocampal facilitation and posttetanic potentiation and the RNA response to stimulation have been shown to be phenomena which depend on this K⁺ release, and have been attributed a role in learning.     

《行政处罚决定书》有效性与合法性的探讨

药品、医疗器械《行政处罚决定书》的质量 ,一定程度上反映执法者依法行政、依法执法的能力和水平 ,体现执法者专业、综合知识运用和掌握程度 ,进一步显示执法者工作的法律性、规范性和责任性。行政处罚行为并非任何条件下都有效 ,它必须符合法定程序和条件 ,否则 ,就会导致《行政处罚决定书》无效、可变更或被撤销。本文就如何保证《行政处罚决定书》的有效性、合法性 ,做一些初步探讨。1　建立四级审核负责制即案件有关人员按照分工 ,各负其责 ,层层把关 ,杜绝差错 ,将《行政处罚决定书》实行多级审核。案件主办人负责对《行政处罚决定书…     

异维A酸治疗中、重度痤疮的疗效观察

目的：观察和评价异维A酸胶丸（泰尔丝）治疗中、重度痤疮的临床疗效和安全性。方法：选择中、重度痤疮患者102例,给予异维A酸20mg/d,分2次服,服至4wk后,视病情改为10mg／d,1次服用,连续服至12wk停药,判断疗效。患者每10d接受疗效观察1次,记录皮损形态及数目变化,直至疗程结束,并同时记录副反应。在服用异维A酸治疗期间,停用其它治疗痤疮的药物。对较大的囊肿合并积脓者,可配合局部处理。结果：中度痤疮患者总有效例数为83例,重度患者的总有效例数为17例,中度和重度痤疮患者的合计总有效例数为100例,总有效率为98％。结论：异维A酸用于痤疮的治疗,尤其是中、重度痤疮治疗效果显著。     

力骨胶囊防治大鼠实验性骨质疏松症的药效学

目的研究力骨胶囊预防和治疗维甲酸致大鼠骨质疏松症的药效学。方法采用维甲酸致大鼠实验性骨质疏松模型 ,随机分组给药 ,检测实验鼠股骨密度、断裂载荷、湿重、干重等物理指标及相关生化指标。结果力骨胶囊能明显提高模型大鼠的股骨密度和断裂载荷 ,显著增加模型大鼠血清Ca、P、Mg水平 ,降低模型大鼠血清ALP水平及羟脯氨酸与肌酐比值 ,并增加模型大鼠的股骨湿重、干重、灰重、体积、长度、直径等。结论力骨胶囊可有效地预防和治疗维甲酸诱导的大鼠实验性骨质疏松     

谈药品的属性和分类

将药品特征与药品属性结合起来，从自然属性、社会属性、法律属性和商品属性对药品加以描述，并将产品分类和药品属性相结合，以提高对药品概念的总体认识。     

Studies on the non-pathogenicity of Chryseobacterium proteolyticum and on the safety of the enzyme: protein-glutaminase

Protein-glutaminase (PG) is a protein-deamidating enzyme produced from the microorganism Chryseobacterium proteolyticum strain 9670. Food safety studies were conducted on both the enzyme and the production organism. The strain was evaluated for pathogenicity and toxigenicity by intravenous and oral inoculation studies in Slc:ICR male SPF mice. The results demonstrate that the tested C. proteolyticum strain is of very low pathogenicity comparable to known food source bacterial strains and is very unlikely to demonstrate any pathogenicity in animals or humans. The level of endotoxin is very low and typical of the endotoxin levels in drinking water and teas. A 90-day study of PG, conducted in Sprague-Dawley rats, showed no adverse effects due to the enzyme up to dose levels of 2500 mg/kg-bw/day (NOAEL). Details of the study are presented, including, organ and body weights, histological findings, and blood and urine chemistry. Additionally, bacterial reverse mutation test (Ames test) and chromosomal aberration test using mammalian established cell line were conducted, resulting in the absence of mutagenicity in PG.     

海洋真菌多糖YCP对小鼠扶正减毒作用的研究

从海洋真菌YC中提取的真菌多糖YCP,选择9,3,1 mg/kg的不同剂量,分别联合60Co放疗和Cy化疗正常小鼠和Heps荷瘤鼠,观察药物对放、化疗的减毒作用。以荷瘤小鼠观察药物对小鼠的扶正作用。结果:YCP(9,3,1 mg/kg)剂量组可显著地对抗由大剂量Cy造成的正常小鼠外周血白细胞,骨髓有核细胞数和胸腺指数的下降(P<0.01,P<0.05)。YCP(9,3 mg/kg)剂量组可显著地抑制由大剂量Cy和60Co照射造成的Heps荷瘤小鼠外周血白细胞,骨髓有核细胞数和脾脏指数和胸腺指数的下降(P<0.01,P<0.05)。YCP(9,3 mg/kg)可显著提高S180荷瘤小鼠的吞噬指数k和血清半数溶血值(P<0.01,P<0.05)。结论YCP可明显对抗由60Co照射,大剂量化疗药Cy引起的正常和荷瘤小鼠的血液和骨髓抑制毒性。YCP可显著提高S180荷瘤小鼠免疫功能。     

Influence of enhancers on the absorption and on the pharmacokinetics of cefodizime using in-vitro and in-vivo models

In the development of novel antibiotics, more and more compounds have been found that cannot be absorbed orally and, therefore, must be administered intravenously or intramuscularly. Because of the obvious drawbacks of drug delivery by injection, the development of alternatives with enhanced oral bioavailability has received much attention in pharmaceutical research. Cefodizime, a novel third-generation cephalosporin with significant advantages in the parenteral treatment of common infections, was used as a model drug. Cefodizime behaves as a highly hydrophilic compound, as shown from its extremely low partition coefficient. The effect of cationic absorption enhancers (hexadecyldimethylbenzylammonium chloride, N-hexadecylpyridinium bromide, dodecyltrimethylammonium bromide and hexadecyltrimethylammonium bromide) on the lipophilicity of cefodizime was investigated by means of the n-octanol/water system. Results showed that the counter-ions had a positive influence on the solubility of cefodizime. These results on partitioning coefficients in the n-octanol/buffer system were confirmed using an in-vitro transport model with artificial and biological membranes (Caco-2-cells). Furthermore, the physiological compatibility of the absorption enhancers was investigated using the active D-glucose transport. The pharmacokinetic profile of cefodizime was evaluated in rabbits after intraduodenal administration with and without an absorption enhancer.     

复合海绵的细胞毒性及生物相容性研究

目的评价复合海绵的细胞毒性及生物相容性。方法采用MTT实验考察复合海绵浸提液对L929细胞增殖的抑制作用;扫描电镜观察L929细胞在海绵表面的生长情况;利用分光光度法测定其对鼠抗凝血的溶血作用;在鼠肝脏造成活性出血创面,用复合海绵或明胶海绵止血后,光镜观察海绵与肝脏组织的相容性。结果复合海绵浸提液对L929细胞增殖无抑制作用,该细胞可在海绵表面正常生长;无溶血作用,组织相容性较好。结论复合海绵无细胞毒性,且具有良好的生物相容性。     

Studies on the time course and the effect of cholinergic and adrenergic receptor blockers on the stimulus effect of nicotine

This study investigated the stimulus property of nicotine in the rat. The primary objectives of the study were 1. to determine the time course of the nicotine stimulus and its relationship to brain levels of the drug and 2. to determine whether the nicotine stimulus is dependent upon the integrity of specific neurotransmitter systems. A lever choice discrimination was used. After injection of nicotine, depression of one lever in an operant test chamber resulted in food reinforcement according to a variable interval schedule of 15 sec. When saline was administered, the opposite lever was reinforced. A high degree of discriminated responding was observed when either 400 g/kg or 200 g/kg of nicotine was used as a discriminative stimulus. The degree of discrimination decreased as the length of the time period between the injection of nicotine and the test of discrimination was increased. This decline in discrimination was similar to the decline in brain levels of nicotine suggesting that nicotine discrimination is directly related to the concentration of nicotine in the brain. Atropine, mecamylamine, dibenamine, propranolol and -methyl-para-tyrosine (AMPT) were all tested, in a range of doses, for effects upon nicotine discrimination. Of these, only mecamylamine antagonized the nicotine stimulus. These results indicate that the stimulus effect of nicotine is mediated specifically through nicotinic-cholinergic receptors and not muscarinic-cholinergic or adrenergic receptors.A preliminary report of this investigation appeared in the Pharmacologist 15, 452 (1973).