静脉滴注赖氨匹林治疗发热患者的疗效观察

目的比较静脉滴注赖氨匹林与复方氨林巴比妥注射液、对乙酰氨基酚片对发热患者的退热疗效。方法选择发热患者120例,随机分成三组,每组40例。A组给予赖氨匹林注射剂0.9g加入0.9%生理盐水100ml静脉滴注;B组给予复方氨林巴比妥注射液（安痛定）2ml肌肉注射;C组给予对乙酰氨基酚片0.5g口服。三组病例用药30min,60min,120min各测体温1次,观察退热疗效。结果赖氨匹林组退热效果最快,用药30min,体温降至（38.5±0.2）℃,总有效率82.5%;用药60min体温降至（37.7±0.3）℃,总有效率90%;用药120min体温降至（36.6±0.4）℃,总有效率95%。在相同条件下,赖氨匹林的退热疗效高于复方氨林巴比妥和对乙酰氨基酚。结论静脉滴注赖氨匹林退热效果快,不良反应小,是理想、安全的退热药物,值得临床推广。     

Effect in the rhesus monkey of salicylate on centrally-induced endotoxin fevers

Fever was induced in the rhesus monkey by micro-injecting Escherichia coli into the rostral hypothalamus. A similar dose of this bacterial pyrogen given intravenously failed to increase body temperature. Sodium salicylate, given intragastrically during the plateau phase of the pyrexic response, reduced or abolished the experimentally-induced fever but had no effect on the body temperature of the afebrile monkey. These data suggest that the antipyretic activity of the salicylate was mediated by an antagonism to the action of the pyrogen within the CNS.     

Inhibition of brain cyclooxygenase-2 activity and the antipyretic action of nimesulide

The antipyretic action and the mechanism of action of 4-nitro-2-phenoxymethanesulfonanilide (nimesulide), a new nonsteroidal antiinflammatory drug, were investigated in yeast-induced febrile rats. Yeast-injected rats developed marked fever and exhibited an approximately 7-fold increase in brain levels of prostaglandin E₂ and an approximately 2-fold increase in the expression of cyclooxygenase-2 mRNA despite an almost unchanged expression of cyclooxygenase-1 mRNA. Nimesulide produced a dose dependent antipyretic action, which was stronger than that of indomethacin and ibuprofen, and decreased dose dependently the increased brain prostaglandin E₂ levels, whereas it did not influence the expression of cyclooxygenase-2 mRNA. It inhibited markedly the enhanced brain cyclooxygenase activity, primarily cyclooxygenase-2, in vivo and dose dependently increased brain cyclooxygenase activity in vitro. These results suggest that the marked antipyretic action of nimesulide is primarily mediated through the selective inhibition of the activity of brain cyclooxygenase-2 induced under febrile conditions.     

复方野菊感冒冲剂的清热抗炎止咳作用

目的 观察复方野菊感冒冲剂的清热抗炎止咳作用.方法 动物随机分为5组,对照组,ig.等体积水;阳性组,ig.阿斯匹林100mg/kg(咳必清10mg/kg);给药组,分别ig.复方野菊感冒冲剂3g/kg、6g/kg、12g/kg,每天给药1次,连续7天.观察对大鼠酵母发热和角叉菜胶足跖肿胀以及小鼠咳嗽潜伏时间和咳嗽次数的影响.结果 复方野菊感冒冲剂可显著抑制大鼠发热和足跖肿胀,明显延长小鼠咳嗽潜伏时间和减少咳嗽次数.结论 复方野菊感冒冲剂具有明显的清热止咳作用.     

Inhibition of interleukin 1 (IL-1)-elicited leukocytosis and LPS-induced fever by soluble immune response suppressor (SIRS)

IL-1-induced leukocytosis was inhibited or blocked in a dose-dependent manner by SIRS, an antigen-nonspecific suppressive lymphokine, when administered intravenously or per os to CBA mice. Timing experiments showed that SIRS effectively inhibited the leukocytosis when administered within 30 minutes of the IL-1. An antipyrogenic activity of SIRS was observed in rabbits injected intravenously with LPS. SIRS, given intravenously in one or two doses, markedly reduced LPS-induced fever. SIRS (2000 units) was a more effective antipyretic agent than aspirin (3 mg/kg body weight, intramuscularly). The results suggest that SIRS may be a potential drug for use in IL-1-mediated disorders.     

扑热息痛滴鼻剂对小儿退热作用的临床观察

本文观察了扑热息痛滴鼻剂治疗４００例小儿发热的临床效果。以扑热息痛片剂为对照组。观察组和对照组的总有效率分别为９４％和８８％，无显著性差异（Ｐ＞０．０５）；高效率（３０ｍｉｎ内体温降至３７℃以下）分别为７３％和３％，有极显著性差异（Ｐ＜０．０１）。说明滴鼻剂的起效明显优于片剂，而疗效无明显差别。     

Mechanism of inhibition of prostaglandin H synthase by eugenol and other phenolic peroxidase substrates

The mechanism of inhibition of prostaglandin H synthase (PHS) by eugenol was investigated using purified apoenzyme reconstituted with either manganese protoporphyrin IX (Mn-PHS) or hematin (Fe-PHS). Eugenol stimulated Fe-PHS activity at low concentrations and inhibited at higher concentrations, an activity typical of many phenolic compounds. Eugenol was also an excellent reducing cosubstrate for the peroxidase, being cooxidized to a reactive quinone methide in the process. Higher concentrations of eugenol were required to inhibit Fe-PHS than Mn-PHS (which retains cyclooxygenase activity but not peroxidase activity). Inhibition by eugenol was highly dependent on arachidonic acid concentration. In experiments using Mn-PHS, eugenol increased the time required for the initiation of O2 consumption after addition of arachidonic acid and also inhibited the rate of O2 uptake. Eugenol did not, however, affect the total amount of O2 consumed. The addition of 10 microM hydroperoxide (prostaglandin G2) to these incubations did not prevent the inhibitory effects of eugenol. Other phenolic compounds, including guaiacol, butylated hydroxyanisole, and acetaminophen inhibited Mn-PHS in a manner similar to eugenol. These results demonstrate that eugenol and other phenolic compounds specifically inhibit the cyclooxygenase component of PHS and that this inhibition occurs in addition to, or independent of, the effect of these compounds on peroxide tone or their peroxidative metabolism. We suggest that this inhibition is due to competition with arachidonic acid for the active site of PHS.     

尼美舒利解热镇痛抗炎作用比较研究

目的研究尼美舒利的解热、镇痛、抗炎作用的量效关系,比较尼美舒利3种药理作用的ED50为临床合理使用尼美舒利提供依据。方法分别采用热灭活大肠埃希菌制备家兔发热模型、冰醋酸制备小鼠疼痛模型、角叉菜胶诱发大鼠足跖肿胀模型,观察尼美舒利的解热、镇痛、抗炎作用,并计算ED。结果尼美舒利能显著降低家兔体温,减少小鼠扭体次数,明显减轻大鼠足关节肿胀程度,其解热、镇痛、抗炎作用的ED50分别为0.85～1．95,2.56,3.15～4.05mg·kg^-1,根据体表面积比例换算成人ED50分别为0．50～0.60,2.72,0.26～0.59mg·kg^-1。结论尼美舒利发挥解热、镇痛和抗炎作用的ED,n存在差异,其中解热最低。     

Pharmacology of a new non-steroidal anti-inflammatory agent 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo-(3,2-b)(1,3)-benzoxazin-9-one (W-2395)

W-2395, a new heterocyclic compound, is an orally effective anti-inflammatory, analgesic and antipyretic agent. It is active in adjuvant-induced polyarthritis when given prophylactically or therapeutically. W-2395 also inhibits carrageenan-induced hind paw edema in the rat, an activity which is not altered by adrenalectomy or hypophysectomy. The analgesic activity of W-2395 is superior to that of acetylsalicylic acid or phenylbutazone, while its antipyretic activity in rats with yeast-induced fever is equivalent to aspirin. Unlike other useful anti-inflammatory agents, W-2395 does not produce ulcers when given in effective doses, nor does it cause gastrointestinal blood loss as measured by the excretion of ⁵¹Cr-tagged red blood cells. However, at lethal doses ulcerogenicity was observed. W-2395 has a weak diuretic effect which most likely does not contribute to its anti-inflammatory action.     

黄芩上清口服液主要药效学研究

目的研究黄芩上清口服液的抗炎、解热、镇痛和体外抑菌作用。方法采用小鼠耳壳肿胀法,伤寒、副伤寒甲乙三联菌苗导致家兔发热反应以及小鼠扭体法观察黄芩上清口服液的抗炎、解热、镇痛作用,采用平皿二倍稀释法测定黄芩上清口服液的最低抑菌浓度(M IC)。结果黄芩上清口服液抑制二甲苯所致小鼠耳壳肿胀及醋酸所致小鼠扭体反应,并具有明显的抑制伤寒、副伤寒甲乙三联菌苗所致家兔发热反应作用;黄芩上清口服液对6株菌的M IC范围为13.5~432 mg/m l。结论黄芩上清口服液具有明显的抗炎、解热、镇痛及体外抑菌作用。     

黄芩上清口服液主要药效学研究

目的研究黄芩上清口服液的抗炎、解热、镇痛和体外抑菌作用.方法采用小鼠耳壳肿胀法,伤寒、副伤寒甲乙三联菌苗导致家兔发热反应以及小鼠扭体法观察黄芩上清口服液的抗炎、解热、镇痛作用,采用平皿二倍稀释法测定黄芩上清口服液的最低抑菌浓度（MIC）.结果黄芩上清口服液抑制二甲苯所致小鼠耳壳肿胀及醋酸所致小鼠扭体反应,并具有明显的抑制伤寒、副伤寒甲乙三联菌苗所致家兔发热反应作用;黄芩上清口服液对6株菌的MIC范围为13.5～432 mg/ml.结论黄芩上清口服液具有明显的抗炎、解热、镇痛及体外抑菌作用.     

Effects of intracerebroventricular floctafenine and indomethacin on body temperature in febrile rabbits.

1. We injected the potent prostaglandin synthesis inhibitors, floctafenine and indomethacin, intravenously and intracerebroventricularly in rabbits made febrile by intravenous injection of leucocyte pyrogen. 2. Floctafenine (75 mumol) injected intravenously failed to affect the fever, whereas indomethacin (15 mumol) markedly reduced the fever. 3. When injected into the cerebral ventricles, floctafenine was feebly antipyretic, and then only at a dose ten times the antipyretic dose of indomethacin. 4. Our results support the suggestion that floctafenine has no antipyretic action when administered peripherally. However, its lack of antipyretic effect cannot be explained solely on the grounds that it fails to cross the blood-brain barrier.     

金钮扣醇提物中解热、镇痛有效部位的研究

目的 研究金钮扣醇提物中不同部位的解热镇痛作用.方法 提取金钮扣醇提物,按极性大小依次用石油醚、氯仿、乙酸乙酯、正丁醇萃取,按提取部位分为空白对照组、阳性组、金钮扣醇提组、石油醚萃取组、氯仿萃取组、乙酸乙酯萃取组、正丁醇萃取组和水层组.用干酵母致热法观察其对发热大鼠的分时段解热作用,用热板法和扭体法观察其对小鼠外周性镇...     

基于UPLC-Q-Exactive Orbitrap-MS联合网络药理学探究双黄连解热抗炎的作用机制

目的:基于UPLC-Q-Exactive Orbitrap-MS方法,利用网络药理学和分子对接技术初步探究双黄连解热抗炎的物质基础及作用机制.方法:利用UPLC-Q-Exactive Orbitrap-MS技术鉴定双黄连口服液中的主要化学成分.基于网络药理学,将已定性化合物录入Swiss Target数据库筛选成分靶点...     

Prenatal tolerability of acetaminophen and other over-the-counter non-selective cyclooxygenase inhibitors

Over-the-counter cyclooxygenase inhibitors are used to relief fever and various types of acute pain like headache, toothache, earache, sore throat, as well as postoperative and menstrual ones. They are also major ingredients in cold and flu mixtures. Unlike well-known organ toxicological profile, their prenatal toxicity was not fully established. For a long time, acetaminophen was considered as a relatively safe antipyretic and analgesic drug during pregnancy. However, a new data indicate that it may increase the risk of cryptorchidism and asthma during childhood as well as preeclampsia, preterm birth, maternal phlebothrombosis and pulmonary embolism. Contrary to acetaminophen, non-selective cyclooxygenase inhibitors (non-steroidal anti-inflammatory drugs - NSAID; i.e., diclofenac, ibuprofen, naproxen) may induce intrauterine growth retardation, ductus arteriosus constriction with secondary persistent pulmonary hypertension, reduced fetal renal perfusion that led to oligohydramion, prolonged pregnancy as well as increase prevalence of intracranial bleeding in newborns. Furthermore, a higher risk of miscarriage, stillbirth and some congenital malformations (cardiac and diaphragmatic defects, celosomy - gastroschisis and umbilical hernia) was reported for non-selective inhibitors, in particular high doses of acetylsalicylic acid (aspirin).     

埃必定的抗炎作用

目的研究埃必定的抗炎作用，为埃必定应用于临床提供理论基础。方法应用鼠耳肿胀、角叉菜胶足肿胀、佐剂性关节炎、角叉菜胶气囊模型观察埃必定的抗炎作用，用酵母致热模型观察埃必定的解热作用并对胃肠道溃疡形成进行观察。结果埃必定对鼠耳肿胀、角叉菜胶足肿胀和佐剂性关节炎均有明显抑制作用。对炎症性渗出、白细胞游走和毛细血管通透性增高均有明显抑制作用。对酵母引起的体温升高有退热作用。胃肠道粘膜毒性较吲哚美辛低。结论埃必定具有抗炎、解热作用，此作用与吲哚美辛相似，但对胃肠道粘膜溃疡形成作用却远低于吲哚美辛。     

The antipyretic effects of aminopyrine and sodium acetylsalicylate on endotoxin-induced fever in rabbits (author's transl)

The antipyretic effects of aminopyrine and sodium acetylsalicylate on endotoxin-induced fever in rabbits were studied relative to the route and dose of administration. Intravenous administration of aminopyrine produced a marked antipyretic effect, intracisternal administration produced a lesser effect and i.v. was the effective route. Similar results were obtained in the nonfebrile rabbits. On the contrary, the intracisternal administration of sodium acetylsalicylate reduced the body temperature to the same degree both in febrile and nonfebrile rabbits, but sodium acetylsalicylate given i.v. to nonfebrile rabbits did not reduce the body temperature. 4-aminoantipyrine and N-acetyl-4-aminoantipyrine, the major metabolites of aminopyrine had a lesser effect in the febrile rabbits. Antipyretic effects of sodium salicylate, the metabolite of sodium acetylsalicylate were similar to the effects of sodium acetylsalicylate. These data suggest that the antipyretic effects of aminopyrine may not be involved in the CNS, while the antipyretic effects of salicylate may be due to a direct action on the CNS.     

Effect of antipyretics on polymorphonuclear leukocyte functions in children

The aim of this study was to investigate whether fever and antipyretic drugs had an adverse effect on human polymorphonuclear leukocyte (PMN) functions (phagocytic and intracellular killing activity). Twenty febrile children with an axillary temperature of 39-40 degrees C and 20 healthy children without fever were included. Polymorphonuclear leukocytes were isolated. The effects of in vitro addition of antipyretic drugs (acetaminophen, metamizole sodium, nimesulid and ibuprofen) on PMN functions were tested. Phagocytic activity was assayed by the ingestion of yeast cells by PMNs and intracellular killing activity by the ingestion of yeast cells (stained blue) killed by PMNs. PMNs derived from febrile children exhibited better phagocytic activity when ibuprofen was added. In contrast, phagocytic activity was enhanced when acetaminophen, metamizole sodium or nimesulid was added in children without fever. Intracellular killing activity was enhanced when ibuprofen or metamizole sodium was added in children without fever. We conclude the antipyretic drugs at safely achievable concentrations do not suppress PMN function in vitro.     

Spizofurone (AG-629) increases gastric mucosal blood flow in dogs: A possible mechanism of its anti-ulcer effect

The effect of spizofurone (AG-629), a new anti-ulcer agent, on gastric mucosal blood flow was investigated in anesthetized dogs and the effects were compared with those of prostaglandin E₂. Intravenous administration of spizofurone in doses of 15 and 30 mg/kg caused a dose-related increase in gastric mucosal blood flow. Spizofurone (1–10 mg/ml) given intragastrically for 15 min produced a sustained increase in gastric mucosal blood flow in a concentration-dependent manner; with 3 mg/ml there was about a 50% increase in gastric mucosal blood flow at the peak and a 2 h duration of action. The mode of action of spizofurone was similar to that of prostaglandin E₂. The reduction in the gastric mucosal blood flow as induced by indomethacin was markedly improved by spizofurone. The topical action of spizofurone was confirmed in an in situ experiment using a stomach flap fixed to a lucite chamber. These results indicate that spizofurone increases gastric mucosal blood flow after systemic and topical administration, and this increase in gastric mucosal blood flow would account for the anti-ulcer effects of this drug.     

消炎退热颗粒清热解毒作用研究

目的：观察中成药消炎退热颗粒（DPZG）对家兔发热模型、小鼠急性耳廓肿胀模型、小鼠内毒素血症模型的作用,探讨其清热解毒的作用和机理。方法：采用脂多糖（lipopolysaccharides,LPS）耳缘静脉注射建立家兔发热模型,评价其解热作用;采用二甲苯致小鼠急性耳廓肿胀模型评价其抗炎作用;建立小鼠内毒素血症模型,观察DPZG对于D-氨基半乳糖（ACTD）敏化小鼠LPS致死攻击的影响,评价其抗内毒素的作用;以Elisa法检测DPZG对内毒素血症模型小鼠血清中TNF-α、IL-1β等炎症因子水平的影响,Western blot法检测小鼠肝、脾、肾组织中膜突蛋白（moesin）以及磷酸化P38 MAPK表达。结果：与模型组比较,DPZG对家兔体温升高有显著抑制作用,与阿司匹林趋同;可显著降低二甲苯致小鼠急性耳廓肿胀程度;可显著升高内毒素血症模型小鼠存活率;显著降低小鼠血清中TNF-α、IL-1β水平和小鼠肝脾肾组织内p-P38MAPK和膜突蛋白（moesin）的表达,效果明显优于中成药对照药蒲地蓝消炎口服液（PBKH）。结论：消炎退热颗粒有显著清热解毒作用,主要作用方式是解热、抗炎、抗内毒素,且效果明显优于PBKH。其作用机制可能与抑制IL-1β、TNF-α、Moesin以及p-P38 MAPK的表达有关。