Arachidonic acid metabolites in CSF in hypoxic-ischaemic encephalopathy of newborn infants

The aim of this study was to evaluate the cerebral synthesis of eicosanoids in the asphyctic newborn and to investigate the relation between the prostanoid profiles in cerebrospinal fluid (CSF) and the appearance and severity of hypoxic-ischaemic encephalopathy (HIE). Levels of 6-keto-PGF _1-α, TXB₂, PGE₂ and PGF_2-α in CSF were measured in 40 full term newborns during the first day of life. Thirty of these newborns had birth asphyxia and were divided into three groups: 10 without HIE, 12 with mild HIE and 8 with moderate-severe HIE. They were compared to a control group of 10 non-hypoxic newborns. Determinations of the metabolites in CSF were performed by RIA and expressed as pg/ml (mean ± SD). The CSF TXB₂ (thromboxane A₂ metabolite) in asphyxiated newborns was always higher than in the control group (28.12 ± 10.6), and related to the severity of HIE ( p = 0:005): without HIE (50.84 ± 16.4; p = 0:02), mild HIE (80.65 ± 12.64; p ± 0:01) and moderate-severe HIE (178.14 ± 20.5; p < 0:01). The CSF 6-keto-PGF _1-α (prostacyclin metabolite) in asphyxiated newborns was always higher than in the control group (80.55 ± 12.56), but indirectly related to the severity of HIE: without HIE (240.95 ± 28.12; p < 0:01), mild HIE (183.65 ± 30.1; p < 0:01) and moderate-severe HIE (140.55 ± 25.12; p < 0:01). In the moderate-severe HIE group, the increase in TXB₂ was higher than the rise in 6-keto-PGF _1-α.     

萘普生对大鼠着床期宫内PGF_(2α)含量及宫内节育器抗生育作用的影响

本文测定了对照组及两个萘普生(前列腺素合成酶抑制剂)处理组大鼠着床期宫内PGF2α的含量。结果表明,对照组、萘普生低剂量组(2mg/kg体重)和高剂量组(20mg/kg体重)的PGF2α含量分别为6.71±0.93、2.19±0.34和1.01±0.18ng/100g组织(三组间P<0.01)。同时,还观察到在本实验条件下,萘普生无明显干扰节育器抗生育作用,药物本身亦未呈现显著抗生育活性。     

消炎痛及乙胺嗪对动物急性缺氧性肺、脑血管反应的影响

研究消炎痛及乙胺嗪对家兔肺、脑血管和大鼠脑微动脉缺氧反应的影响。发现吸入10％氧使家兔肺血管阻力(PVR)增加,脑血管阻力(CVR)降低,大鼠脑微动脉扩张。用消炎痛明显增强家兔缺氧性肺、脑血管反应。△PVR％由用药前26.6±16.7％增至44.2±7.7％;△CVR％则由一12.9±4.5％减至-30.7±4.7％;大鼠微动脉直径增大率(△D％)由用药前28.2±2.0％增至41.3±5.8％;用乙胺嗪则使缺氧时△PVR％由 84.6±18.1％降至 23.8±8.5％;△CVR％由-16.7±4.5％变为 6.9±2.8％;△D％由 29.7±5.8％减至 25.6±5.0％。结果表明前列腺素在缺氧性肺血管收缩反应及脑血管扩张反应中起调节作用,而白三烯则在缺氧性肺血管收缩反应中起介导作用。     

适量饮酒对健康成年男性血浆TXB2,6-Keto-PGF2a及血小板聚集功能的影响

①目的　观察适量饮酒对健康成年男性的血小板聚集功能及血浆血栓素B2 (TXB2 ) ,6 酮 前列腺素F2a(6 Keto PGF2a)的影响。②方法　将 80例健康成年男性随机分成 4组 ,分别空腹饮用矿泉水、啤酒、干红葡萄酒各 2 0 0mL ,白酒 50mL加矿泉水至 2 0 0mL .于饮前及饮后 2h分别测定血小板的聚集率及解聚率 ,并采血测定血浆TXB2 ,6 Keto PGF2a.③结果　矿泉水组饮后上述指标无变化 (t=0 .0 3～ 0 .84,P >0 .0 5) ;白酒、啤酒、红葡萄酒组饮后血小板聚集率减低 (t=8.1 2～ 2 4 .39,P <0 .0 1 ) ,解聚率升高 (t=2 8.48～ 35 .2 2 ,P <0 .0 1 ) ,血浆TXB2 降低 (t=2 5 .69～ 89.83 ,P <0 .0 1 ) ,而血浆 6 Keto PGF2a升高 (t=2 1 .0 6～ 2 3 .2 9,P <0 .0 1 )。④结论　健康成年男性适量饮酒可减低其血小板聚集功能 ,降低其血浆TXB2 ,提高其血浆 6 Keto PGF2a水平     

Short-term indomethacin administration does not impair excretion of acute potassium load in humans

Maintenance treatment with prostaglandin synthesis inhibitors often causes some degree of hyperkalemia, indicating impaired potassium (K) excretion. Hypoaldosteronism probably is a mediating factor, but it is unknown whether these drugs also impair renal K excretion directly. Indomethacin, for example, stimulates NaCl reabsorption in Henle's loop, and thus may impair K excretion by decreasing distal NaCl delivery. We therefore studied the effect of 1 day administration of indomethacin (50 mg tid) on the excretion of a single oral KCl (1 mmol kg-1 body weight) in six healthy volunteers taking a 40 mmol sodium diet. To allow analysis of renal sodium handling, clearance studies were performed during water loading. In this acute setting, indomethacin had no effect on plasma K, and did not decrease plasma aldosterone. However, indomethacin clearly reduced NaCl excretion. Nonetheless, the excretion of the K load was entirely normal. Excretion of the K load was accompanied by increased clearance of phosphate and uric acid, and natriuresis. Data derived from the maximal free water clearance were compatible with increased delivery to and decreased reabsorption from the diluting segment. Occurrence of these effects was not prevented by indomethacin, although overall NaCl excretion remained less than observed without indomethacin. Indomethacin reduced prostaglandin E2 excretion substantially. Apparently, in normal man indomethacin does not impair K excretion directly, even though it greatly reduces NaCl excretion. Moreover, the effects of K on renal NaCl handling, probably contributing to the excretion of a K load, are not dependent on renal prostaglandins.     

动物与临床胆道梗阻和胆道炎症时胆管组织PGI_2和TXB_2的变化

采用放射免疫法测定实验性胆道炎症兔胆系组织以及几种胆道疾患病人胆系组织中６－ｋｅｔｏ－ＰＧＦ１α与ＴＸＢ２的含量。结果显示：动物模型组与病人组的上述两指标均显著增高；ＡＯＳＣ病人的ＴＸＢ２增高更明显，而胆道梗阻病人胆管组织无此变化。提示前列腺素类及血栓素对胆道炎症的发生可能有关，ＴＸＢ２的负性作用尤为重要。     

Central tumour necrosis factor-α mediates the early gastrointestinal motor disturbances induced by lipopolysaccharide in sheep

Cytokines are involved in fever and other symptoms of the acute phase response induced by endotoxins. The aim of this work was to study the involvement of central tumour necrosis factor-alpha (TNF-alpha) in the changes induced by lipopolysaccharide (LPS) on gastrointestinal (GI) motility in sheep. Body temperature and myoelectric activity of the antrum, duodenum and jejunum was recorded continuously. Intravenous (i.v.) administration of LPS (0.1 micro g kg-1)-induced hyperthermia, decreased gastrointestinal myoelectric activity and increased the frequency of the migrating motor complex (MMC). These effects started 40-50 min after LPS and lasted for 6-7 h. TNF-alpha (50 and 100 ng kg-1) mimicked these effects when injected intracerebroventricularly (i.c.v.) but not i.v. Pretreatment with soluble recombinant TNF receptor (TNFR:Fc, 10 micro g kg-1, i.c.v.) abolished the TNF-induced actions and reduced those evoked by LPS. Furthermore, the effects induced by either LPS or TNF were suppressed by prior i.c.v. injection of indomethacin (100 micro g kg-1). In contrast, the i.v. injections of TNFR:Fc or indomethacin were ineffective. Our data suggest that LPS disturbs GI motility in sheep through a central pathway that involves TNF-alpha and prostaglandins sequentially.     

Down-regulation of natural killer cell activity by autologous polymorphonuclear leucocytes

It has been recently reported that neutrophils are involved in the regulation of NK cell activity. However, the mechanism of such regulation is unclear. The present study was designed to investigate the mechanisms involved in the regulation of NK cytotoxicity by human neutrophils. The role of indomethacin, an anti-inflammatory drug, in this interaction was studied. NK cells were purified from peripheral blood obtained from normal individuals. NK cell cytotoxicity was tested on K 562 cell line by Cr release assay. Autologous neutrophils obtained from peripheral blood were stimulated by opsonized zymosan either in the presence or absence of indomethacin. The role of neutrophil supernatant containing oxygen radicals and prostaglandins on NK cytotoxicity was examined. It was shown that supernatants from stimulated neutrophils significantly inhibited (P less than 0.05) the autologous NK cell cytotoxicity. The presence of indomethacin in the in vitro reaction mixture, or given orally to donors, partially or completely abolished the inhibitory effect of neutrophil supernatant. Indomethacin inhibited prostaglandin E2 release, and luminol-enhanced, myeloperoxidase-mediated chemiluminescence of activated PMN. Diafiltration of neutrophil supernatant showed that the inhibitory activity was present in the fraction containing molecules lower than 5,000 daltons. In conclusion, our findings indicate that down-regulation of NK cytotoxicity is mediated by prostaglandins produced by stimulated neutrophils and possibly by oxygen radicals.