The roles of prostaglandin E2 and D2 in lipopolysaccharide-mediated changes in sleep

When living organisms become sick as a result of a bacterial infection, a suite of brain-mediated responses occur, including fever, anorexia and sleepiness. Systemic administration of lipopolysaccharide (LPS), a common constituent of bacterial cell walls, increases body temperature and non-rapid eye movement (NREM) sleep in animals and induces the production of pro-inflammatory prostaglandins (PGs). PGE₂ is the principal mediator of fever, and both PGE₂ and PGD₂ regulate sleep–wake behavior. The extent to which PGE₂ and PGD₂ are involved in the effect of LPS on NREM sleep remains to be clarified. Therefore, we examined LPS-induced changes in body temperature and NREM sleep in mice with nervous system-specific knockouts (KO) for the PGE₂ receptors type EP₃ or EP₄, in mice with total body KO of microsomal PGE synthase-1 or the PGD₂ receptor type DP, and in mice treated with the cyclooxygenase (COX) inhibitor meloxicam. We observed that LPS-induced NREM sleep was slightly attenuated in mice lacking EP₄ receptors in the nervous system, but was not affected in any of the other KO mice or in mice pretreated with the COX inhibitor. These results suggest that the effect of LPS on NREM sleep is partially dependent on PGs and is likely mediated mainly by other pro-inflammatory substances. In addition, our data show that the main effect of LPS on body temperature is hypothermia in the absence of nervous system EP₃ receptors or in the presence of a COX inhibitor.     

川芎嗪对脑外伤患者血栓素、前列腺环素及颅内压的影响

28例重度脑外伤患者分为川药嗪治疗组和一般治疗对照组,两组病人均于用药前和用药后3小时测定血浆和脑室内脑脊液(VCSF)中血栓素代谢产物(TXB_2)前列腺环素代谢产物6—酮—PGF_(la)(6KP)和颅内压。结果表明:两组治疗前血浆、VCSF中TXB_2及T/K均明显高于正常献血员对照组,川芎嗪能降低脑外伤患者血浆、VCSF中TXB_2及T/K值,对颅内压则无明显影响。提示川芎嗪能抑制脑外伤对血小板的激活、纠正循环血中TXA_2—PGI_2平衡失调,从而改善脑微循环。     

Pulmonary and haemodynamic effects of extracorporeal circulation in the cat and the beneficial effects of prostacyclin

Side-effects of a veno-venous extracorporeal system and possible beneficial effects of prostacyclin (epoprostenol) are analyzed on the cat. Three groups were studied; one control group without extracorporeal circulation and two groups with an extracorporeal flow of 10–12 ml/kg/min, one of which was given prostacyclin (70–110 ng/kg/min). The extracorporeal circulation triggered a decrease in arterial saturation (from 99 to 91 %) and carbon dioxide elimination (increase in arterial to end-tidal PCO₂ by about 1 kpa) a metabolic acidosis (pH7.20), a platelet consumption (50%) and shortened survival time, side-effects reduced by prostacyclin. Further, there was a marked increase in haemoglobin concentration indicating hypovolemia via capillary fluid filtration. None of these side-effects were seen in the control group. Extracorporeal circulation as a trigger for pulmonary dysfunction and for impaired tissue nutrition with possible beneficial effects of prostacyclin is discussed, and also from a clinical point of view (i.e. extracorporeal lung assistance, ECLA), on the basis of the results.     

Effects of aspirin on nasal responses in atopic subjects

Preliminary experiments indicated that solutions of aspirin (ASA) in buffered saline, pH 7.35, did not significantly change nasal airways resistance (NAR) when 0.1 ml of solution containing 22.5 mg (or less) per deciliter was sprayed into each nostril. Subsequently it was shown that this quantity of ASA administered intranasally did not significantly change NAR responses 15 min later to intranasal administration of increasing concentrations of histamine, methacholine, or an irritant (NH₃ gas). However, the same atopic subjects demonstrated significantly decreased responses to intranasal challenge with short ragweed extract (SRW) after intranasal ASA. In addition, prior oral administration of ASA, Na salicylate, and indomethacin significantly inhibited nasal challenge responses to SRW in sensitive subjects under controlled conditions.     

Prävalenz des Plasmafaktormangels in der Wiener Bevölkerung

Summary A screening investigation for the presence of risk factors for the development of atherosclerosis demonstrates a plasma factor deficiency in 0,8% in the Viennese population. These findings are in agreement with the data of a newborn screening performed earlier. All the persons were clinically healthy. In 4 of them at least 1 family member suffered from the same defect. The pathogenetic relevance of the plasma factor defect for thrombophilia at young age is discussed.

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Abkürzungsverzeichnis VIP Viennese Initiative for Prostaglandin - PGI2 Prostazyklin - PG Prostaglandin - PF Plasmafaktor - PRP pättchenreiches Plasma - HUS hämolytischurämisches Syndrom - PF4 Plättchenfaktor 4 - TG Thromboglobulin - TXB2 Thromboxan B2 Diese Untersuchung im Rahmen des VIP(VienneseInitiative forProstaglandin)-Screenings wurde vom Medizinisch-Wissenschaftlichen Fonds des Bürgermeisters der Bundeshauptstadt Wien unterstützt     

妊娠高血压疾病与偶联因子、前列环素的相关性研究

目的通过对不同程度、不同孕周妊娠高血压疾病患者、正常孕妇血管内皮细胞活性物质—偶联因子6(CF6)、前列环素I2(PGI2)的检测,探讨其与妊娠高血压疾病发病的相关性。方法选择妊娠高血压疾病患者36例作为研究组,再选同期与之孕周、年龄相匹配的正常孕妇33例作为对照组,采用放射免疫方法检测CF6、PGI2的血浆含量。结果研究组CF6水平明显高于对照组,分别为491.5±95.3(pg/ml);255.3±75.5(pg/ml),两组比较,P<0.01,有极显著性差异;研究组PGI2水平低于对照组,分别为133.5±76.7pg/ml;216.6±89.1(pg/ml),P<0.05,有显著性差异。研究组平均动脉压(MAP)、产时出血量多于对照组,而新生儿体重、Apgar评分均低于对照组,P<0.01,有显著性差异。结论CF6、PGI2两种血管活性物质的失调可能在妊娠高血压疾病的形成过程产生重要的作用。     

Prostacyclin formation in undelayed and delayed pig flank flaps

Summary A specific 6-keto-prostaglandin PGI₂ radioimmunoassay (R.I.A.) was used to follow tissue prostacyclin formation in a series of acute and delayed pig flaps. Each flap measured 12×5 cm and four white, female ehester pigs, averaging 21 kgs in weight, were used. Flap tissue samples were taken at day 0 (control) 1–8, 10, 14, 17 and 21 using 0.4 mm diameter cork borer. Prostacyclin formation started to rise on day 4 and extended until the 10th day in both types of flaps. The hyperemic circulation that occurred following delay procedure is associated with a rise in prostacyclin production whereas the higher rise in prostacyclin in the undelayed flap is due to the reactive inflammation.     

KMG03粉针剂对大鼠实验性急性心肌缺血的保护作用

采用结扎大鼠冠脉造成急性心肌缺血模型。观察KMG03粉针剂的抗心肌缺血作用。结果：KMG03粉针剂50mg/kg和100mg/kg对大鼠实验性急性心肌缺血均有一定程度的保护作用。在改善心电图S——T段的上移、降低血清CPK,LDH方法两个剂量组均有显著作用。在缩小心肌塞范围方面,以100mg/kg组为明显,KMG03粉针剂和丹参均能保护超氧化物岐化酶活性,显著降低丙二醛含量,还能显著增加缺血心肌前列环素合成。结果表明：KMG03粉针剂对心肌缺血的保护作用与抗脂质过氧化作用有关,其促进前列环素合成作用可能与其抗心肌缺血有关。     

Dual action of angiotensin II on coronary resistance in the isolated perfused rabbit heart

Summary We studied the functional role of angiotensin II (AII) receptor subtypes and vasodilatory endothelial autacoid release in response to AII in isolated perfused rabbit hearts. AII infusion induced biphasic changes in coronary perfusion pressure (CPP): an initial increase was followed by a decrease until a plateau was reached. At higher concentrations of AII (10 nmol/l) this plateau phase was lower than the initial CPP level. AII infusion elicited inverse changes in peak left ventricular pressure (LVP): coronary constriction was associated with a transient decline, and during the plateau phase LVP was clearly increased. AII also moderately augmented prostacyclin (PGI₂) release from the coronary vascular bed. The AII-induced changes in CPP, LVP, and PGI₂ release were effectively inhibited by the AT₁ receptor subtype antagonist ICI D8731 (30 nmol/l), but not by the AT₂ receptor antagonist CGP 42112 (30 nmol/l). The adenosine A₁ receptor antagonist 8-phenyltheophylline (0.1 mol/l) attenuated the decline in CPP following the constriction phase without affecting the changes in LVP during AII infusion. The cyclooxygenase inhibitor diclofenac (1 mmol/l) had no effect on the AII-induced changes in CPP, whereas the nitric oxide-synthase inhibitor N^G-nitro-L-arginine (30 mol/l) markedly potentiated the vasoconstriction but was without effect on the plateau phase of the response. In contrast to AII, the thromboxane analogue U46619 elicited sustained increases in CPP which were associated with slight decreases in LVP.In conclusion, AII induced a biphasic pressor response in the rabbit coronary vascular bed consisting of a transient vasoconstriction followed by a dilatation especially at higher concentrations of AII, an effect which was independent of the endothelial autacoids nitric oxide and PGI₂. The AII-induced dilatation probably reflected rapid desensitization of the coronary arterial smooth muscle to the constrictor effect, and the concomitant accumulation of vasodilatory metabolites such as adenosine, generated during the positive inotropic action of AII. All the effects of AII in the rabbit heart appeared to be mediated via the AT, receptor subtype localized on coronary endothelial and smooth muscle cells, as well as on cardiomyocytes.On leave from the Department of Biomedical Sciences, University of Tampere, P.O. Box 607, FIN-33101 Tampere, FinlandCorrespondence to: I. Pörsti     

Septischer Schock und multiples Organversagen in der chirurgischen Intensivmedizin

Zusammenfassung Beschrieben wird ein tierexperimentelles Sepsismodell, das der Problematik chirurgischer Intensivpatienten entspricht. Nach rezidivierender Applikation von E.-coli-Endotoxin W0111:134 unter standardisierten Bedingungen konnten spezifische hämodynamische, biochemische (TNF, TXA₂, PG I₂, IL-6, PAF) und morphologische Veränderungen (pulmonales Endothel) nachgewiesen werden. Die sepsisinduzierten ARDS-Veränderungen werden mit einer Hochfrequenzdruck-und-flowmessung mit 385 Meßpunkten fiber einem Atemzyklus analysiert. Die Rolle des Darms in der Sepsis wurde mit ionenselektivem Kaliummonitoring vergleichend auf der Mukosa and Serosa untersucht. Jede Endotoxingabe wurde vom Dünndarm mit selektiven Anstiegen der Kaliumaktivität als Ausdruck einer Endotoxin-induzierten relativen Ischämie beantwortet. Das Profil der Oberflächenkaliumwerte korreliert sowohl mit dem cardiaco output als auch mit den Prostazyklinspiegeln. Die während der Versuchsdauer kontinuierlich abnehmende Mukosa-Serosa-Kaliumdifferenz kann als Nachweis einer die Sepsis katalysierenden intestinalen Permeabilitätsstörung interpretiert werden.

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Septic shock and multiple organ failure during surgical intensive care. Evaluation of pulmonary and intestinal dysfunction assessment in a porcine model

The study deals with an animal model for the problems of surgical intensive care patients. Following repeated applications of E. coli endotoxin W0111:134 under standard conditions, specific hemodynamic and biochemical (TNF, TXA₂, PGI₂, IL-6, PAF) and morphological (endothelium of the lung) alterations were detected. ARDS patterns induced by the sepsis were analyzed by high-frequency measurement of pressure and flow (385 measurements per breathing cycle). The role of the intestine in sepsis was investigated by ion-selective monitoring of surface potassium activity comparing mucosa and serosa. Every injection of endotoxin was followed by a selective increase of the potassium activity revealing relative ischemia induced by the endotoxin. The profile of the potassium levels on the surface correlates both with the cardiac output and with the prostacyclin levels. The continuous narrowing of the difference between mucosa and serosa, potassium during the period of investigation can be regarded as evidence for pathologic change in permeability fostering the septic course.