多粘菌素B琼脂糖层析柱清除体液中内毒素

用多粘菌素B琼脂糖亲和层析法清除内毒素,结果表明:5ml多粘菌素B层析柱的总吸附内毒素能力为450 μg,用此法可完全清除体液或各种液体中的内毒素,对血清及腹水中的内毒素也有明显的吸附作用,而其他各种主要成分(除内毒素外)经过处理后无明显改变。去氧胆酸是一种强有力的去污剂,可使已饱和的柱子复活,复活率达85％左右。该方法有简便,可靠,吸附能力大,柱子的复活率高等优点。本方法的建立为内毒素血症的治疗展示了新的前景。     

Synthesis and biological activities of novel 5-(2-acylethynyl)uracils

5-(2-Acylethynyl)-2,4-dimethoxypyrimidines (3-6) were synthesized in excellent yields from 2,4-dimethoxy-5-[2-(trimethylsilyl)ethynyl]pyrimidine (2) by treatment with acid chlorides in the presence of anhydrous aluminum chloride. Compounds 3-6 were deblocked with chlorotrimethylsilane and sodium iodide in acetonitrile to the corresponding 5-[(2-acyl-1-iodo)vinyl]uracils (7-10), which on treatment with potassium hydroxide in dioxane yielded the corresponding 5-(2-acylethynyl)uracils (11-14). The 5-(2-acylethynyl)uracils were found to be active against Ehrlich ascites carcinoma (EAC) cells in vivo, the most active compounds being 5-(2-benzoylethynyl)uracil (11) and 5-(2-p-toluoylethynyl)uracil (12). The T/C values of 281 and 300 were obtained for compounds 11 and 12, respectively, in the case of mice bearing EAC cells. The 5-(2-acylethynyl)uracils have also shown in vitro activity against CCRF-CEM and L1210/0 tumor cell lines. The lead compound 5-(2-p-toluoylethynyl)uracil effectively inhibited thymidylate synthetase.     

Quantitative structure-activity relationships in MAO-inhibitory 2-phenylcyclopropylamines: Insights into the topography of MAO-A and MAO-B

Ten (E)-and (Z)-isomers of 2-phenylcyclopropylamine (PCA), 1-Me-PCA, 2-Me-PCA, N-Me-PCA, and N, N-diMe-PCA and fifteeno ⁻, m⁻, p⁻ isomers of (E)-PCA with substituents of Me, Cl, F, OMe, OH were synthesized in this laboratory and tested for the inhibition of rat brain mitochondrial MAO-A and MAO-B. The effects of substituents, their positions, and stereochemistry on the inhibition were assessed for the compounds with substituents at cyclopropyl and amino groups and QSAR analyses were performed using the potency data of ring-substituted compounds. The best correlated QSAR equations are as follows: pI₅₀=0.804 Π² Blo−1.069 Blm+0.334 Lp−1.709 HDp+7.897 (r=0.945, s=0.211, F=16.691, p=0.000) for the inhibition of MAO-A; pI₅₀=1.815 π-0.825 Π² R+0.900 Es²+0.869 Es³+0.796 Es⁴−0.992 HDp+0.562 HAo+3.893 (r=0.982, s=0.178, F=23.351, p=0.000) for the inhibition of MAO-B. Based on the potency difference between stereoisomers of cyclopropylamine-modified compounds and on QSAR results, it is proposed that the active sites of MAO-A are composed of one deep hydrophobic cavity near para position, two hydrophobic cavities interacting with Me group, a hydrophobic area accomodating phenyl and cyclopropyl backbone, steric boundaries, a hydrogen-acceptor site near para position, and an amino group binding site and that in addition to the same two hydrophobic cavities, hydrophobic area, steric boundaries, hydrogen-acceptor site, and amino group binding site, another steric boundary near para position and a hydrogen donating site near ortho position constitute active sites of MAO-B.     

Changes of Intestinal Caicitonin Gene-related Peptide in Acute Intestinal Radiation Sickness in Rats

The characteristic distribution of calcitonin gone-related peptide(CGRP)inthe small intestine of rats and its changes in acute intestinal radiation sickness(AIRS)were studied with immunocytochemistry(whole mount stretch preparations of the smallintestine and cryostat sections)and radio-immunoassay.It was found that in all the lay-ers of the intestinal walls,there were large amounts of CGRP immunoreactive(CGRP-I)nerve fibers which existed in especiaUy high density in the myenteric,submucosal andmucosal plexuses.There was also a rather high density of the nerves around the smallvessels of the small intestine and the intestinal crypts.Some CGRP-I neurons were seenin the myenteric and submucosal plexuses.In AIRS,the intestinal CGRP showed a dip-hasic change,in a lower level in the 24th h and a higher level in the 48th and 72nd h af-ter irradiation.The results indicate that CGRP may be related to the regulation of the motility,se-cretion,absorption,sensation,and regional blood flow of the gastrointestinal tract.Pro-bably,CGRP is released under the stress of AIRS and participates in the mechanism ofinjury through many ways especially through the influence on the regional blood flowand the increase of the permeability of blood vessels.     

定坤丹的显微鉴定研究

对定坤丹(蜜丸)进行了显微鉴定研究,将29种组成药物全部检出,对各组成药物的显微鉴别特征作了简明描述,并附显微特征图。     

CT-guided stereotactic injection of radionuclide in treatment of brain tumors.

140 patients with brain tumor were treated by CT-guided stereotactic injections of radionuclides, such as Aurum-198 (198 Au), Phosphorus-32 (32 P) and Yttrium-90 (90Y). Of these patients aged from 3 to 67 years (average 37), 64 were male and 76 female. Astrocytoma was found in 75 patients, craniopharyngioma in 46, metastatic carcinoma in 7, meningioma in 5, germinoma in 4 and pituitary adenoma in 3. The tumors were located in the deep part or functionally critical area of the brain. After 267 times of injection of colloidal isotopes, no major adverse effects or complications occurred. Follow-up for 6 to 48 months showed improvement in symptoms in 104 (74.3%) patients and CT scanning showed the diminished tumors.

     

自制新荧光剂EPQS的性能测试

作者对自制新荧光剂EPQS进行了性能测试。结果:量子产率为0.21;最大激发波长和荧光波长分别为375nm和484nm,stokes位移109nm;检测生物化合物常用的缓冲溶液对荧光峰位无影响,对荧光强度影响很小;温度的影响也小(18～43℃,FRI61.5～58.1),PH的影响也不大。说明EPQS不仅荧光参数好,而且稳定性也好。适合在较广泛的环境条件下使用。