N-ω-Carbethoxypentyl-4-quinolones: A New Class of Leukotriene Biosynthesis Inhibitors

6-[(4-Quinolinyl)oxy]hexanoic acids and the corresponding esters were designed and synthesized as inhibitors of the production of arachidonic acid metabolites. The inhibitory activities were assayed in vitro by evaluation of serum leukotriene B₄ and thromboxane B₂ production. While all 6-[(4-quinolinyl)oxy]hexanoic acids and their esters proved to be inactive, the N-alkyl-4-quinolones, obtained as by-products in their synthesis, were found to be a new class of leukotriene biosynthesis inhibitors.     

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Actions on αT3-1 Gonadotrophs Show Desensitization

PACAP is a hypothalamic hypophysiotropic factor that acts upon a number of pituitary cells, including gonadotrophs. In the gonadotroph-derived αT3-1 cell line, PACAP acts via PVR1 receptors to stimulate adenylyl cyclase and phosphoinositidase C. PACAP-stimulated cAMP accumulation is inhibited by protein kinase C-activating phorbol esters in these cells and the current work was undertaken primarily to establish whether it is also subject to homologous regulation. In acute experiments, PACAP27-stimulated cAMP accumulation (intracellular plus extracellular) was measured (in the presence of phosphodiesterase inhibitor) both in intact cells and in cell membranes. The peptide increased cAMP accumulation, but initial rates of PACAP27-stimulated cAMP accumulation were reduced to between 10 and 50% within 10 min of stimulation in both cells and membranes. The initial rate of forskolin-stimulated cAMP accumulation was maintained in membranes but not in intact cells (although the deviation from linearity was less pronounced than with PACAP27). Thus, rapid homologous desensitization to PACAP27 occurs in intact αT3-1 cells, but is not entirely receptor specific. Rapid homologous desensitization of PACAP27-stimulated cAMP accumulation also occurred in the presence of a protein kinase C activating phorbol ester, which inhibited cAMP accumulation without altering the kinetics of the PACAP27 effect. Brief pre-treatment (3 min) with PACAP27 also reduced the ability of PACAP27, but not gonadotrophin-releasing hormone, to cause a spike-type elevation of cytosolic Ca²⁺ concentration (a consequence of phosphoinositidase C activation). In chronic desensitization studies, pre-treatment for 6 h with PACAP27 caused a dose-dependent (IC₅₀ approximately 10 nM) reduction of PACAP-stimulated cAMP accumulation and down regulated cell surface PVR1 receptors (to approximately 50%). Thus, it appears that PACAP27-stimulated (PVR-1 receptor mediated) adenylyl cyclase undergoes rapid homologous desensitization in αT3-1 cells, which is paralleled by homologous desensitization of PACAP27-stimulated phosphoinositidase C activity and involves mechanisms distinct from those underlying heterologous desensitization by phorbol esters. Chronic desensitization of PACAP-stimulated cAMP accumulation and down-regulation of cell surface PVR-1 receptors also occurs in these cells although the receptor loss may not entirely explain the observed desensitization.     

Characterization of “plasma proteins” secreted by cultured rat macroglial cells

The brain is isolated behind a blood-tissue barrier that restricts the access of circulating proteins to neural cells. There is evidence that some of these proteins are synthesized within the central nervous system. The present study examines the synthesis and secretion of such proteins by cultured macroglial cells. Primary glial cultures were derived from cortical and subcortical regions of neonatal rat brains, and subsequent secondary cultures were enriched in type-1 astrocytes, type-2 astrocytes, or oligodendrocytes. Newly synthesized proteins were immunoprecipitated from the culture media using antisera directed against whole rat serum. All three types of glial cells secreted a range of plasma proteins. In general, type-1 astrocytes secreted more of these proteins than did type-2 astrocytes or oligodendrocytes, although the one-dimensional polyacrylamide gel electrophoresis (PAGE) profiles were specific for each cell type. Antisera directed against specific plasma proteins identified three of the most abundant proteins secreted by type-1 astrocytes as transferrin, α-2-macroglobulin, and ceruloplasmin. Northern blot analysis of cellular RNA confirmed that type-1 astrocytes contained transferrin mRNA, and that it was more abundant in cultures derived from subcortical regions than from cortical regions. In situ hybridization studies revealed that virtually all type-1 and type-2 astrocytes contained transferrin mRNA. Since the proteins identified in this study have been proposed to have a variety of neurotrophic roles in the central nervous system, these data further extend the range of possible functions that glial cells may serve in the CNS.     

Immunohistochemical Study of Colorectal Polyps with Antibodies against CEA,CA19-9, CA125, CA15-3 (DF3), PCNA and p53

Abstract: We analyzed the expression of CEA, CA19-9, CA125, CA15-3 (DF3), PCNA and p53 immunohistochemically in 14 tissue specimens of mucosal cancers in adenoma, seven tubulovillous adenoma specimens, and 16 tubular adenoma specimens. The rates of positive staining for mucosal cancer in adenoma, tubulovillous adenoma and tubular adenoma specimens, respectively, were: for CEA: 100%, 85.7% and 75%; for CA19-9: 71.4%, 71.4% and 56.2%; for CA125:0%, 0% and 0%;for CA15-3 (DF3): 64.3 %, 0% and 0 %; for PCNA: 100%, 88.9% and 56.2%; and for p53: 35.7%, 0% and 0% . The results suggest that the expressions of CEA, CA19-9, CA15-3 (DF3), PCNA and p53 are related to colorectal tumorigenesis. None of the specimens studied showed staining for CA125, suggesting that CA125 is not involved in the early stages of colorectal carcinogenesis. There was no significant difference in the rates of positive staining for CEA and CA19-9 among mucosal cancer in adenoma, tubular adenoma and tubulovillous adenoma specimens. However, the rates of positive staining for PCNA and p53 were significantly higher in mucosal cancer in adenoma specimens than for tubular adenoma specimens (p<0.05), and the rate of CA15-3 (DF3) positive staining was significantly higher for mucosal cancer in adenoma than for tubulovillous adenoma (p<0.01) and tubular adenoma (p< 0.001) specimens. Therefore, the CA15-3 (DF3) antigen is an immunohistochemical marker for colorectal carcinomas. The present results suggest that CA15-3 (DF3), PCNA and p53 play important roles in the genesis of colorectal adenomas.     

Gingival crevicular fluid IL-8: correlation with local IL-1β levels and patient estrogen status

Gingival crevicular fluid (GCF) IL-8 and IL-1,1β levels were determined by sandwich enzyme-linked immunosorbent assays. Associations between IL-8 and IL-1β GCF levels, and between these cytokines and patient estrogen status were evaluated. IL-8 and IL-1β were detected more frequently and in higher amounts/30 s GCF sample in estrogen-deficient patients than in estrogensufficient patients. IL-8 and IL-1β GCF levels were significantly correlated. These lindings suggest that GCF IL-8 levels are associated with patient estrogen status and local IL-1β concentrations.     

OK-432增强人腹腔抗癌免疫功能的研究

目的　探讨腹腔内注射OK - 4 32增强腹腔免疫功能的机制。方法　选择非炎症和非肿瘤手术患者作为实验对象 ,实验组分别于手术前 72小时、4 8小时和 2 4小时腹腔内注射 4KE的OK - 4 32。开腹后采集腹腔内巨噬细胞 ,并用人胃癌MKN1细胞作为靶细胞对巨噬细胞的癌细胞毒性进行分析。同时采集大网膜 ,对大网膜乳斑的数量和面积进行了观察分析。结果　OK - 4 32显著增加了腹腔内巨噬细胞的数量 (P <0 .0 5 )、增强了巨噬细胞的吞噬活性和酶活性 (P <0 .0 5 )、增加了NO的分泌和巨噬细胞的癌细胞毒性 (P <0 .0 5 ) ,以及大网膜乳斑的数量和面积 (P <0 .0 5 )。结论　手术前腹腔内注射OK - 4 32可以作为预防癌细胞腹腔内种植转移的有效方法。     

左双腔支气管导管管端位置与吸气峰压变化的关系

目的 观测无隆突钩双腔支气管导管(DLT)管端位置与吸气峰压(Ppeak)以及肺顺应性环形状改变的关系，探讨用Ppeak和顺应性环的变化评估DLT管端位置的可行性。方法 拟行右侧剖胸手术的成年患者32例，静脉诱导后插入左Mallinckrodt DLT，吸入氧化亚氮和地氟醚维持麻醉。按纤维支气管镜(FOB)确认DLT管端位置和通气方式将观测过程分为四个阶段：第一阶段(S1)，管端位置正确的双肺通气；第二阶段(S2)，管端位置正确的左侧单肺通气；第三阶段(S3)，管端插入左下支气管(置管过深)的左侧单肺通气；第四阶段(S。)，管端处在左支气管开口(置管偏浅)的左侧单肺通气。每阶段均机械通气15min。结果 回归方程预计插管深度与FOB检查符合者占71．9％。S2时Ppeak值比S1时增加50．8％，肺顺应性(Cdyn)值减少36．2％；S3时Ppeak值比S1时增加87．4％，Cdyn值减少56．8％。PV环曲线斜率向右明显移位，环体显著延长。结论 用无隆突钩DLT行肺隔离，在无FOB定位的条件时，联合应用听诊法、回归方程预计插管深度、动态监测气道峰压和P-V环的变化综合评估，可提高DLT管端的正确到位率。单肺通气的气道峰压超过双肺通气时的1．65倍，且气道峰压超过25cm H2O．应高度怀疑DLT管端发生过深移位。     

Effect of psychotomimetics and some putative anxiolytics on stress-induced hyperthermia

Summary Stress-induced hyperthermia (SIH), which is seen in the last mice removed from the cage, is a novel animal model sensitive to anxiolytic drugs. SIH is antagonized by CL 218872 (25 and 50 mg/kg, os), by tracazolate (5 and 7.5 mg/kg, ip) and by 2-AP-5 (50 and 100 mg/kg, ip). At higher dose, CL 218872 (100 mg/kg, os) and tracazolate (12.5 mg/kg, ip) lose their activity.PK 9084 (5–40 mg/kg, ip) and CGS 9896 (2–20 mg/kg, both ip and os) were also ineffective in preventing SIH. The anti-hyperthermic effect of CL 218872 (25 mg/kg) and tracazolate (7.5 mg/kg) was blocked by the benzodiazepine antagonist Ro 15–1788 (15 mg/kg). CGS 9896 (10 mg/kg, os) also reversed the effect of CL 218872 (25 mg/kg) on SIH.Differently from anxiolytics, MK-801 (0.5–1 mg/kg, os), PCP (2.5 mg/kg, ip) and d-amphetamine (10 mg/kg, ip) evoked hyperthermia in the first set of mice and prevented a further stress-induced rise of body temperature in the last set of mice.     

中药合654-2治疗重度黄疸型肝炎42例

我院自2001年1月-2005年12月，在常规综合治疗的基础上采用中药合654-2治疗重度黄疸型肝炎42例，疗效较满意，报道如下。