精氨酸加压素对家兔血细胞生成内生致热原的影响

本文观察了精氨酸加压素对体外培育的兔全血细胞产生内生致热原的影响。结果表明，ＡＶＲ对内毒素诱生ＥＰ过程有明显抑制作用；而ＡＶＰ单独与血细胞培养无降温物质产生；同时，所用剂量的ＡＶＰ对ＥＰ性发热无直接抑制作用。因此作者认为，ＡＶＰ１能够抑制ＥＴ诱生家兔血细胞生成ＥＰ，这可能是其降低或阻断ＥＴ性发热的主要机制之一。     

精氨酸加压素在内毒素热限形成中的作用

本文观察了家兔静脉注射不同剂量ＥＴ后中隔区，下丘脑组织及血浆中ＡＶＰ含量的变化。结果显示：在ＥＴ发热过程中，中隔区，下丘脑及血浆ＡＶＰ含量均显著增多（Ｐ＜０．０１）；ＥＴ发热达热限时，体温不再升高，中隔区与血浆ＡＶＰ含量也不再增多，且中隔区及血浆ＡＶＰ含量变化与体温变化呈明显正相关（ｒ＝０．９８４，０．０５＜Ｐ＜０．０１；ｒ＝０．９９４，Ｐ＜０．０１）；此时，下丘脑升高的ＡＶＰ含量开始下降（Ｐ０。     

家兔葡萄球菌性发热及其热限的探讨

采用加热杀死的白色葡萄球菌菌体作激活物,给家兔耳缘静脉注射,观察剂量-发热效应,血浆EP的活性以及血浆和脑脊液中cAMP含量变化。结果表明,在一定的范围内,随剂量递增,发热效应相应加强,但达到一定浓度,可出现热限;发热时,血浆可检出循环EP;血浆致热活性,脑脊液cAMP含量随发热效应增强而升高,出现热限时,则不再升高。作者推论:cAMP可能是葡萄球菌性发热的重要中枢介质;EP的产生释放受限和体温调节中枢内cAMP的产生受限可能是构成葡萄球菌性热限的重要因素。     

大鼠内生致热原性发热时不同脑区精氨酸加压素和亮氨酸脑咖啡肽含量的变化

本实验用大鼠静脉注射内生致热原（ＥＰ）复制发热模型。观察发热反应及发热不同时相、不同胞区精氨酸加压素（ＡＶＰ）和亮氨酸脑啡肽（Ｌ－ＥＫ）含量的变化。结果表明：大鼠ＥＰ双相热时下丘脑组织ＡＶＰ含量在双峰热的两个高峰期和体温恢复期均明显高于对照组，ＡＶＰ含量与发热第一时相和第二时相体温升高有相关关系。而脑干和大脑皮质组织中ＡＶＰ含量则无明显变化。下丘脑组织、脑干组织中Ｌ－ＥＫ含量在双峰热的两个高峰期均高于对照组，恢复期脑干组织中Ｌ－ＥＫ含量仍高于对照组。大脑皮质组织中Ｌ－ＥＫ含量无明显变化。提示ＥＰ性发热时中枢的ＡＶＰ和Ｌ－ＥＫ可能参与体温调节反应。     

Pyrogen retention by highly permeable synthetic membranes during in vitro dialysis

Pyrogen permeability of the new highly permeable synthetic membrane polyethersulfone (DIAPES) was compared to polysulfone in vitro dialysis experiments with heparinized human donor blood in the blood compartment. After sterile dialysis for 5 min, dialysate was contaminated with a culture filtrate of Pseudomonas aeruginosa using high and moderate challenge doses (Limulus assay reactivity 20,000 EU/ml and 50 EU/ml, respectively). Whole blood samples were separated from the blood compartment during the sterile (5 min) and contaminated (60 min) phases of dialysis and incubated for 6 h at 37 degrees C. Blood samples were lysed, and interleukin-1beta and tumor necrosis factor alpha were measured by specific ELISAs. Moderate dialysate contamination (50 EU/ml) did not induce detectable cytokine production in whole blood. High challenge dose (20,000 EU/ml) induced whole blood interleukin-1beta and tumor necrosis factor alpha production in the blood compartment, which was higher with DIAPES than with polysulfone after 30 min. After 60 min, membrane-dependent differences were no longer detectable. Pyrogen concentrations in the dialysate decreased with time indicating adsorption of cytokine-inducing substances to the dialyzer membrane. Pyrogens adsorbed to dialyzer membranes were resuspended during recirculation of sterile phosphate-buffered saline in the dialysate compartment and retained cytokine-inducing activity as seen from whole blood incubation experiments. DIAPES and polysulfone adsorbed pyrogens in the presence of whole blood. Pyrogen adsorption to the membrane polymer and/or to the protein coat on the membrane prevented the passage of pyrogens in the presence of moderately contaminated dialysate. High grade dialysate contamination caused breakthrough of pyrogens into the blood with DIAPES and polysulfone. In order to reduce the risk of a dialysis-dependent inflammatory response, dialysate of high bacteriological quality (ultrapure dialysate) should be mandatory.     

略谈去除中药静脉注射剂中热原方法

去除中药静脉注射剂中的热原。在生产过程中具有非常重要的意义。根据热原的来源及中药静脉注射剂生产过程中热原产生的途径。结合实际工作的情况。通过对原药材提取液的处理，生产过程的处理，容器和安瓿的处理，达到了中药静脉注射剂能顺利通过“鲎试验法”的检测目的。     

Reduced Febrile Responses to Peripheral and Central Administration of Pyrogen in Aged Squirrel Monkeys

There is long-standing controversy as to whether fever capacity is reduced in aged man. Although loss of this cardinal sign of disease would be an impediment to diagnosis and treatment, there has been no previous research on altered febrile responses using aged primate models. In the present experiments the febrile reaction to IV Salmonella typhosa endotoxin was reduced in monkeys over 14 years old and in one-third of those 10–14 years of age compared with that of younger animals. In response to injections of endotoxin into the lateral cerebral ventricle (ICV), animals over 10 years old showed small or no fevers. Injections of probenecid (ICV), an inhibitor of central inactivation of leukocytic pyrogen and prostaglandin, augmented fever caused by IV and ICV endotoxin and hyperthermia caused by ICV PGE₂ in animals under 10 years of age. However, in older animals probenecid increased fever caused by ICV endotoxin only, although the increased response was still less than one quarter that of younger animals. The results indicate that old squirrel monkeys have decreased febrile responses that may be traced to alterations in central sensitivity to pyrogens.     

热限及热限加致热原负荷时脑脊液及血浆中cAMP含量变化的研究

为探讨内毒素(ET)和内生致热原(EP)热限的机制,在家兔静脉注射非热限与热限剂量的EF或EP后及热限加不同致热原负荷时,用竟争性蛋白结合法检测脑脊液和血浆样品中cAMP的含量。结果发现:(1).脑脊液中cAMP含量随EF性发热效应的增强而升高,到达EP热限后则不再上升,而血浆cAMP含量无类似变化。(2).脑脊液和血浆中cAMP含量均随ET性发热效应的增强而上升,到达ET热限后均不再升高。(3).虽然ET热限的发热水平明显高于EP热限,且EP热限加ET负荷使发热水平超过EP热限;但各组之间脑脊液中cAMP含量却无明显差异。上述结果表明,中枢cAMP生成受限可能既是构成EP热限的重要因素,又是ET热限的一个重要成因。但是除cAMP外,ET热限的构成还与其它因素有关。     

家兔内毒素双相热各期脑脊液和血浆cAMP含量的观察

本研究用静脉注射内毒素复制家兔双相热模型,观察双相热各期颈动脉血浆和脑脊液cAMP含量的变化及其与体温变化的关系,结果如下:1.内毒素非热限剂量一次静脉注射引起典型双相热。脑脊液cAMP含量在两个热相高峰期相应出现两个上升波,间歇期体温下降时,脑脊液cAMP含量相应降低,退热后恢复正常。血浆cAMP含量仅在第一热相增高。2.相关检验表明,脑脊液cAMP含量与体温变化呈显著正相关。血浆cAMP含量仅在第一热相与脑脊液cAMP含量相关。以上结果与内生致热原双相热相似,提示内毒素可能主要通过内生致热原以某种方式影响体温调节中枢cAMP的变化,导致双相热型的出现     

Reduced Febrile Responses to Peripheral and Central Administration of Pyrogen in Aged Squirrel Monkeys

There is long-standing controversy as to whether fever capacity is reduced in aged man. Although loss of this cardinal sign of disease would be an impediment to diagnosis and treatment, there has been no previous research on altered febrile responses using aged primate models. In the present experiments the febrile reaction to IV Salmonella typhosa endotoxin was reduced in monkeys over 14 years old and in one-third of those 10–14 years of age compared with that of younger animals. In response to injections of endotoxin into the lateral cerebral ventricle (ICV), animals over 10 years old showed small or no fevers. Injections of probenecid (ICV), an inhibitor of central inactivation of leukocytic pyrogen and prostaglandin, augmented fever caused by IV and ICV endotoxin and hyperthermia caused by ICV PGE₂ in animals under 10 years of age. However, in older animals probenecid increased fever caused by ICV endotoxin only, although the increased response was still less than one quarter that of younger animals. The results indicate that old squirrel monkeys have decreased febrile responses that may be traced to alterations in central sensitivity to pyrogens.