BACKGROUND & AIMS: :The present study was undertaken to investigate the involvement of prostaglandins in the secretagogue action, observed after intraduodenal administration of rhein anthrone and rhein in rats. After intraduodenal administration of rhein anthrone (50 mg/kg), the active metabolite of sennosides, a very marked increase of secretion was observed compared to control. The amount of secretion was calculated by dividing the total weight of the small intestine, obtained 30 minutes after administration of the drug, by the total length. The effect seen with rhein (50 mg/kg) is far less pronounced than that with rhein anthrone and is not significant when compared with control. Pretreating the animals with indomethacin (15 mg/kg, p.o., 1 hour in advance) or with ibuprofen (15 mg/kg, p.o., 1 hour in advance) largely prevents the secretagogue effect of rhein anthrone, suggesting that prostaglandins play an important role in the observed pharmacological action. This idea is reinforced by the observation that pretreatment with hydrocortisone (50 mg/kg, p.o., 6 hours in advance) is also able to counteract the effect of rhein anthrone. After administration of rhein anthrone, an almost tenfold increase of the tissue content of prostaglandin E2 was observed. Here again, the results with rhein were far less pronounced. It is concluded that prostaglandins play an important role in the secretagogue action of rhein anthrone.

背景与目标： : 本研究旨在研究前列腺素在大鼠十二指肠内给予大黄酸和大黄酸后观察到的促分泌作用。十二指肠内给药大黄酸蒽酮 (50 mg/kg) 后，与对照组相比，观察到分泌明显增加。分泌量是通过将施用药物后30分钟获得的小肠的总重量除以总长度来计算的。大黄酸 (50 mg/kg) 的作用远不如大黄酸蒽酮明显，与对照组相比也不明显。用吲哚美辛 (15 mg/kg，p.o.，提前1小时) 或布洛芬 (15 mg/kg，p.o.，提前1小时) 预处理动物，很大程度上阻止了大黄酸蒽酮的促分泌作用，提示前列腺素在观察到的药理作用中起重要作用。观察到氢化可的松预处理 (50 mg/kg，p.o.，提前6小时) 也能够抵消大黄酸蒽酮的作用，从而强化了这一想法。给予大黄酸蒽酮后，观察到前列腺素E2的组织含量几乎增加了十倍。同样，使用rhein的结果远没有那么明显。结论前列腺素在大黄酸蒽酮的促分泌作用中起重要作用。

BACKGROUND & AIMS: :In a previous study, we developed newly synthesized arylthio derivatives of cyclopentenone prostaglandins (GIF-0642, GIF-0643, GIF-0644, GIF-0745 and GIF-0747), which are neuroprotective against both manganese toxicity in PC12 cells and glutamate toxicity in HT22 cells. In the present study, we showed that these compounds and their lead compound, NEPP11, are potent inducers of glial cell line-derived neurotrophic factor (GDNF) expression in C6 glioma cells and primary astrocytes. These neuroprotective cyclopentenone prostaglandins also induced the gene expression of nerve growth factor and, to a lesser extent, brain-derived neurotrophic factor. The induction of GDNF mRNA was transcription-dependent, and the overexpression of dominant-negative Nrf2 attenuated the ability of the (arylthio)cyclopentenone prostaglandins to stimulate GDNF gene expression. These results suggest that (arylthio)cyclopentenone prostaglandins increase GDNF gene expression partly via the Keap1/Nrf2 pathway. A growing number of reports demonstrate the importance of increasing the amounts of neurotrophic factors, especially GDNF, in neuropathological states. Although the precise mechanisms by which the GIF compounds inhibit cell death are under investigation, an increase in neurotrophic factors may contribute to the diverse pharmacological properties of (arylthio)cyclopentenone prostaglandins in vivo and will make them potentially valuable in the treatment of neurodegenerative disorders.

背景与目标： : 在先前的研究中，我们开发了新合成的环戊烯酮前列腺素的芳基硫代衍生物 (GIF-0642，GIF-0643，GIF-0644，GIF-0745和GIF-0747)，它们对PC12细胞中的锰毒性和HT22细胞中的谷氨酸毒性均具有神经保护作用。在本研究中，我们表明这些化合物及其铅化合物NEPP11是C6神经胶质瘤细胞和原代星形胶质细胞中胶质细胞源性神经营养因子 (GDNF) 表达的有效诱导剂。这些神经保护性环戊烯酮前列腺素还诱导了神经生长因子的基因表达，并在较小程度上诱导了脑源性神经营养因子的基因表达。GDNF mRNA的诱导是转录依赖性的，显性负Nrf2的过度表达减弱了 (芳基硫代) 环戊烯酮前列腺素刺激GDNF基因表达的能力。这些结果表明 (芳基硫代) 环戊烯酮前列腺素部分通过Keap1/Nrf2途径增加GDNF基因表达。越来越多的报道证明了增加神经营养因子量的重要性,尤其是GDNF，在神经病理状态下，尽管GIF化合物抑制细胞死亡的确切机制正在研究中，但神经营养因子的增加可能有助于 (芳基硫代) 环戊烯酮前列腺素在体内的多种药理特性，并将使其在治疗神经退行性疾病中具有潜在的价值。

BACKGROUND & AIMS: Porcine iris sphincter muscle strips contracted in response to carbachol. The tissue contraction was inhibited by prostaglandin (PG) E2 but not by PGF2 alpha. In order to investigate the effect of PGs on the iris cells, the porcine sphincter muscle cells were grown in culture to a confluence and characterized. Using the secondary culture of cells, the effect of PGs on carbachol-induced cell contraction was investigated. Both PGE2 and PGF2 alpha at 100 microM blocked cell contraction completely. The concentration required to inhibit 50% of the maximum contraction in 15 minutes was 10(-6) M for PGE2 and 10(-6)-10(-7) M for PGF2 alpha. Using PGE2 receptor subtype agonists (EP2 agonist, 11-deoxy-16, 16 dimethyl PGE2 and EP3 agonist, sulprostone), PGE2 receptor involved in the inhibition of carbachol-induced contraction was identified to be of the EP2 subtype. In support of this characterization, the addition of PGE2 to cultured porcine sphincter muscle cells increased intracellular cAMP level. The discrepancy in PGF2 alpha effect on carbachol-induced sphincter muscle contraction between iris tissue strips and cultured cells suggests that nonmuscular cells may be involved in the modulation of the PGF2 alpha effect on sphincter muscle cells in vivo.

背景与目标： 猪虹膜括约肌肌条因卡巴胆碱而收缩。前列腺素 (PG) E2抑制了组织收缩，但pgf2α 抑制了组织收缩。为了研究PGs对虹膜细胞的影响，将猪括约肌细胞在培养物中生长至汇合并表征。使用细胞的二次培养，研究了PGs对卡巴胆碱诱导的细胞收缩的影响。100微米处的PGE2和pgf2α 都完全阻断了细胞收缩。在15分钟内抑制50% 最大收缩所需的浓度对于PGE2为10(-6) M，对于pgf2α 为10(-6)-10(-7) M。使用PGE2受体亚型激动剂 (EP2激动剂，11-deoxy-16，16二甲基PGE2和EP3激动剂，舒前列酮)，参与抑制卡巴胆碱诱导的收缩的PGE2受体被鉴定为EP2亚型。为了支持这种表征，向培养的猪括约肌细胞中添加PGE2会增加细胞内cAMP水平。在虹膜组织条和培养细胞之间，pgf2α 效应对卡巴胆碱诱导的括约肌收缩的差异表明，非肌肉细胞可能参与体内pgf2α 效应对括约肌细胞的调节。

BACKGROUND & AIMS: The use of cyclooxygenase inhibitors has been seen to reduce the efficacy of many antihypertensive drugs. However, cyclooxygenase inhibitors are normally non-selective because they affect both vascular tissue, where the endothelial prostanoids exert principally a vasodilatory action, and the kidneys, where they also play an important role in regulating hydroelectrolytic metabolism by redistribution of intraparenchymal flow. To evaluate the relative importance of vascular district in the hypertensive patient, we administered ibuprofen - a drug acting with only a minimal antagonist activity. A group of 20 male hypertensives were randomly allocated, according to a single-blind protocol, to treatment with amlodipine (A, 10 mg/day) or lisinopril (L, 20 mg/day). Blood pressure was significantly reduced after 30 days, with a mean difference of -21.75 mmHg for systolic blood pressure (SBP) (95% confidence interval (Cl)-27.46 to -16.04; P< 0.0001) and -14.

15 mmHg for diastolic blood pressure (DBP) (95% Cl-17.13 to -11.17; P< 0.0001). Brachial artery compliance showed a mean increase of 1.

657 x 10(-7) dyn-1 cm(4) (95% Cl1.188 to 2.126; P<0.001), and forearm resistances showed a mean decrease of -41.

973 mmHg ml(-1)s (95% Cl-75.479 to -8.467; P = 0.017). Changes in compliance were significantly related to those in SBP (r= -0.546; P= 0.013). The administration of ibuprofen (400 mg, three times a day for 3 days) was accompanied by a slight but significant increase in SBP, but not in brachial artery compliance or forearm resistances. Only SBP was affected, showing a mean increase of 4.

25 mmHg (95% Cl:1.26 to 7.24; P = 0.008). There was also reduced urinary excretion of PGI(2) and TXA(2) metabolites. The mean change in 6-keto-PGF(1 alpha) and 2,3-dinor-6-keto-PGF(1 alpha) was 45.

71 ng per g urinary creatinine (uCr) (95% Cl-0.16 to-91.25; P= 0.049) and -73.

17 ng (g uCr)(-1) (95% Cl-38.81 to -107.53; P<0.001), respectively.

The mean decrease in TXA(2) catabolites was highly significant-39.

2 ng (g uCr)(-1) (95% Cl-18.17 to-60.22; P< 0.001) and -102.

87 ng (g uCr)(-1) (95% Cl-61.86 to -143.88; P< 0.001) for TXB(2) and 2,3-dinor-TXB(2), respectively. Our study highlighted an inverse correlation between changes in blood pressure and those in urinary 2,3-dinor-6-keto-PGF(1alpha) excretion, irrespective of antihypertensive regimen. This suggests that, in the hypertensive patient treated with NSAIDs, inhibition of vascular prostanoid synthesis may play an important role in countering the efficacy of an important vascular tone regulatory mechanism.

背景与目标： 已发现使用环氧合酶抑制剂会降低许多抗高血压药物的疗效。然而，环氧合酶抑制剂通常是非选择性的，因为它们既影响血管组织 (其中内皮类前列腺素主要发挥血管舒张作用)，又影响肾脏 (其中它们还通过实质内血流的重新分布在调节水电解代谢中发挥重要作用)。为了评估高血压患者血管区的相对重要性，我们服用了布洛芬-一种仅具有最小的拮抗剂活性的药物。根据单盲方案，将一组20例男性高血压患者随机分配至氨氯地平 (A，10 mg/天) 或赖诺普利 (L，20 mg/天) 治疗。30天后血压明显降低，收缩压 (SBP) 的平均差为-21.75 mmHg (95% 置信区间 (Cl)-27.46至-16.04; P< 0.0001) 和-14。舒张压 (DBP) 为15 mmHg (95% Cl-17.13至-11.17; P< 0.0001)。肱动脉顺应性平均增加1。
657x10(-7) dyn-1 cm(4) (95% Cl1.188至2.126; P<0.001)，前臂抵抗力显示平均下降-41。
973 mmHg ml(-1)s (95% Cl-75.479至-8.467; P = 0.017)。依从性的变化与SBP的变化显着相关 (r = -0.546; P = 0.013)。布洛芬 (400 mg，每天3次，共3天) 的给药伴随着SBP的轻微但显着增加，但肱动脉顺应性或前臂阻力没有增加。仅SBP受到影响，平均增加4。
25 mmHg (95% Cl:1.26至7.24; P = 0.008)。PGI(2) 和TXA(2) 代谢物的尿排泄也减少。6-酮-pgf (1α) 和2,3-二酮-6-酮-pgf (1α) 的平均变化为45。
每克尿肌酐 (uCr) 71 ng (95% Cl-0.16至-91.25; P = 0.049) 和-73。
17 ng (g uCr)(-1) (95% Cl-38.81至-107.53; P <0.001)，
TXA(2) 分解代谢物的平均下降非常显著-39。
2 ng (g uCr)(-1) (95% Cl-18.17-60.22; P <0.001) 和-102
87 ng (g uCr)(-1) (95% Cl-61.86至-143.88; P <0.001) 分别用于TXB(2) 和2,3-dinor-txb (2)。我们的研究强调了血压变化与尿2,3-dinor-6-keto-pgf (1α) 排泄之间的负相关，而与降压方案无关。这表明，在接受NSAIDs治疗的高血压患者中，抑制血管前列腺素合成可能在对抗重要的血管张力调节机制的功效中起重要作用。

BACKGROUND & AIMS: :The study was performed to examine whether indomethacin administered during the initial period of acetic acid-induced gastric ulcer healing affects future ulcer recurrence. Gastric ulcers were produced in rats by subserosal injection of acetic acid. Indomethacin (1 mg/kg/day, orally) administered either alone or concomitant with ornoprostil (50 micrograms/kg/day, orally) was started on the fourth day and continued for 56 days. In rats whose ulcer healed at the 90th day after production of ulcer, endoscopy was done every 30 days to examine recurrence of ulcer. Gastric specimens were obtained 10, 30, 60, 90, and 240 days after ulcer production for histology, to quantitate the height of regenerated mucosa, thickness of fibrous tissue, degree of polymorphonuclear cell infiltration, and PAS-positive cells. Cumulative ulcer recurrence rate was significantly higher in rats initially treated with indomethacin than in controls. Increased polymorphonuclear cell infiltration was the major histologic abnormality persisting after cessation of indomethacin. Ornoprostil reversed these abnormalities caused by indomethacin. In conclusion, the administration of indomethacin during the initial period of the ulcer healing promoted persistent polymorphonuclear cell infiltration and increased ulcer recurrence rates, possibly via a prostaglandin-dependent mechanism.

背景与目标： : 进行这项研究是为了检查在乙酸引起的胃溃疡愈合的初期服用消炎痛是否会影响未来的溃疡复发。通过浆膜下注射乙酸在大鼠中产生胃溃疡。从第4天开始单独或与ornoprostil (50微克/千克/天，口服) 联合给药吲哚美辛 (1 mg/kg/天，口服)，并持续56天。在溃疡产生后第90天溃疡愈合的大鼠中，每30天进行一次内窥镜检查以检查溃疡的复发。在溃疡产生后10、30、60、90和240天获得胃标本进行组织学检查，以定量再生粘膜的高度，纤维组织的厚度，多形核细胞浸润的程度和PAS阳性细胞。最初用吲哚美辛治疗的大鼠的累积溃疡复发率显着高于对照组。多形核细胞浸润增加是吲哚美辛停止后持续存在的主要组织学异常。Ornoprostil扭转了吲哚美辛引起的这些异常。总之，在溃疡愈合初期给予吲哚美辛可能通过前列腺素依赖性机制促进了持续性多形核细胞浸润并增加了溃疡复发率。

BACKGROUND & AIMS: This paper describes the distribution of NAD+-dependent 15-hydroxy prostaglandin dehydrogenase (delta13-reductase) in the mammalian brain and eye tissues. In addition, an NADH-dependent 15-ketoprostaglandin delta13-reductase (15-PGDH) activity was determined in the brain and eye tissue of some species. The rabbit brain and eye tissues were obtained after arterial perfusion with PBS buffer while the monkey, bovine and porcine tissues were obtained without any treatment. [3H]-PGF2alpha or [3H]-15-keto-17-phenyl-18,19,20-trinor-PGF2alpha1-1-isopropy l ester was incubated with different eye tissue preparations under various conditions. No 15-PGDH activity was observed in the monkey brain while 14% of exogenous PGF2alpha was metabolized to its 15-keto-13,14-dihydro-metabolite by the porcine brain. The 15-PGDH activity in the monkey eye tissue was undetectable. Both brain and different eye tissues hydrolysed 15-keto-17-phenyl-18,19,20-trinor-PGF2alpha-1-isopropyl ester to its free acid and the free acid was further metabolized to 15-keto-13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2alpha by the reduction of 13,14-double bond indicating the presence of a delta13-reductase in these tissues. These data suggest that besides the presence of esterases the mammalian brain and eye tissues possess variable amounts of delta13-reductase in spite of their low 15-PGDH activity which may be of importance in physiology and drug metabolism of these tissues.

背景与目标： 本文描述了NAD依赖性15-羟基前列腺素脱氢酶 (delta13-reductase) 在哺乳动物脑和眼组织中的分布。此外，在某些物种的大脑和眼睛组织中确定了NADH依赖性15-酮前列腺素delta13-reductase (15-PGDH) 活性。用PBS缓冲液进行动脉灌注后获得兔脑和眼组织，而无需任何处理即可获得猴，牛和猪组织。[3H]-PGF2alpha或 [3H]-15-酮-17-苯基-18,19，20-trinor-pgf2alpha1-1-异丙基l酯与不同的眼组织制剂在各种条件下孵育。在猴脑中没有观察到15-pgdh活性，而14% 的外源pgf2α 被猪脑代谢为其15-keto-13，14-二氢代谢物。无法检测到猴眼组织中的15-pgdh活性。大脑和不同的眼睛组织都将15-keto-17-phenyl-18，19,20-trinor-pgf2α-1-异丙酯水解为其游离酸，并且游离酸进一步代谢为15-keto-13，14-二氢-17-苯基-18,19，20-trinor-PGF2alpha通过减少13,14-双键表明在这些组织中存在delta13-reductase。这些数据表明，除了酯酶的存在外，哺乳动物的大脑和眼睛组织具有可变量的delta13-reductase，尽管它们的15-pgdh活性较低，这可能在这些组织的生理和药物代谢中很重要。

BACKGROUND & AIMS: :Enzymes involved in prostaglandin I2 (PGI2) and thromboxane A2 (TXA2) synthesis were studied in maternal and fetal platelets and venous endothelium from normotensive pregnant controls (n = 70), women with mild preeclampsia (MP, n = 45), and severe preeclampsia (SP, n = 34). Activities of phospholipase A2 (PHA2), cyclooxygenase (PGHS), and PGI2 synthetase (PGIS) or TXA2 synthetase (TXAS) were determined in platelets and in endothelial cells. The PGHS enzyme was studied further by immunoblot methodology. In maternal platelets: Vmax (per 10(-10) mol/mg protein) and Michaelis-Menten constant (Km) (10(-7) mol, mean +/- SEM) of PHA2 were 3.0 +/- 0.8, 3.0 +/- 0.7, and 31.7 +/- 10.9* maximum velocity (Vmax) and 1.8 +/- 0.3, 2.0 +/- 0.8, and 0.8 +/- 0.2 (Km) in normal control (NC), mild preeclampsia (MP), and severe preeclampsia (SP), respectively (*P less than 0.05 against NC). The apparent overall PGHS plus TXAS activity was 10.2 +/- 1.8, 23.8 +/- 7.1, and 68.8 +/- 18.8* (Vmax) and 3.2 +/- 1.3, 5.4 +/- 1.4, and 6.9 +/- 1.2* (Km, *P less than 0.05 against NC). TXA synthesis in fetal platelets demonstrated PHA2 activity of 6.4 +/- 1.4, 12.0 +/- 1.3, and 17.2 +/- 3.2* (Vmax) and 3.5 +/- 0.9, 2.2 +/- 1.5, and 0.7 +/- 0.3* (Km, *P less than 0.05 against NC), respectively, whereas an apparent overall PGHS plus TXAS activity was 18.5 +/- 2.8, 87.5 +/- 12.5*, and 3.6 +/- 0.1* (Vmax) and 4.8 +/- 1.0, 8.8 +/- 1.2, and 0.8 +/- 0.3* (Km, *P less than 0.05 against NC).(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： : 在血压正常的孕妇对照 (n = 70)，轻度先兆子痫妇女 (MP，n = 45) 和严重先兆子痫的孕妇和胎儿血小板和静脉内皮中研究了参与前列腺素I2 (PGI2) 和血栓烷A2 (TXA2) 合成的酶。子痫前期 (SP，n = 34)。在血小板和内皮细胞中测定了磷脂酶A2 (PHA2)，环氧合酶 (PGHS) 和PGI2合成酶 (PGIS) 或TXA2合成酶 (TXAS) 的活性。通过免疫印迹方法进一步研究了PGHS酶。在母体血小板中: PHA2的Vmax (每10(-10) mol/mg蛋白) 和Michaelis-Menten常数 (Km) (10(-7) mol，平均值 +/- SEM) 为3.0 +/- 0.8，3.0 +/- 0.7，和31.7 +/- 10.9 * 最大速度 (Vmax) 和1.8 +/- 0.3，2.0 +/- 0.8和0.8 +/- 0.2 (Km) 在正常对照 (NC)，轻度先兆子痫 (MP) 和重度先兆子痫 (SP)，分别 (对NC的 * P小于0.05)。表观总体PGHS加TXAS活性为10.2 +/- 1.8、23.8 +/- 7.1和68.8 +/- 18.8 * (Vmax) 和3.2 +/- 1.3、5.4 +/- 1.4和6.9 +/- 1.2 * (Km，* P对NC小于0.05)。胎儿血小板中的TXA合成显示6.4 +/- 1.4、12.0 +/- 1.3和17.2 +/- 3.2 * (Vmax) 和3.5 +/- 0.9、2.2 +/- 1.5和0.7 +/- 0.3 * (Km，* P小于针对NC的0.05)，而明显的总体PGHS加TXAS活性分别为18.5 +/- 2.8、87.5 +/- 12.5*和3.6 +/- 0.1 * (Vmax) 和4.8 +/- 1.0，8.8 +/- 1.2，和0.8 +/- 0.3 * (Km，* P小于0.05对NC)。(抽象截断在250个单词)

BACKGROUND & AIMS: :Paraquat is known to cause severe lung damage through pulmonary edema as its initial feature of toxicity. The purpose of this study was to investigate the toxicity of paraquat in rabbits intraperitoneally injected with 2 or 4 mg/kg/day of the herbicide for a period of 7 days. In the lung, prostaglandin levels of the intoxicated rabbits showed a significant increase in PGF2 alpha. This increase was dose dependent. However, a nonsignificant change in the 6-keto-PGF1 alpha was also observed. Plasma and serum levels of thromboxane-B2 were also significantly elevated but the levels of 6-keto-PGF1 alpha were affected nonsignificantly. The pathology of elevated levels of PGF2 alpha and TXB2 in the lung and blood, in response to paraquat toxicity, is discussed.

背景与目标： : 百草枯已知通过肺水肿引起严重的肺损伤，这是其毒性的最初特征。目的研究百草枯对家兔腹腔注射2或4 mg/kg/天的除草剂，为期7天的毒性。在肺中，中毒兔子的前列腺素水平显示pgf2α 显着增加。这种增加是剂量依赖性的。然而，也观察到6-keto-pgf1α 无显著变化。thromboxane-B2的血浆和血清水平也显着升高，但6-keto-pgf1α 的水平没有显着影响。讨论了响应百草枯毒性的肺和血液中pgf2α 和TXB2水平升高的病理。

BACKGROUND & AIMS: :Rabbit blastocysts recovered at 144 hours post coitum contained the prostaglandins F and E-A. We suggest that one or more of these prostaglandins act as mediators in blastocyst steroidogenesis. (In another study we have demonstrated steroidogenesis in rabbit blastocysts).

背景与目标： : 兔囊胚在coitum后144小时恢复，含有前列腺素F和E-A。我们建议这些前列腺素中的一种或多种在胚泡类固醇生成中起介质作用。(在另一项研究中，我们已经证明了兔胚泡中的类固醇生成)。

BACKGROUND & AIMS: :Amateau and McCarthy's findings published in Nature Neuroscience (June 2004) are noteworthy for suggesting a role for prostaglandins in sexual development. However, evidence suggests that in manipulating PGE2, they unknowingly implicated 3alpha-hydroxysteroid dehydrogenase [E.C. 1.1.1.50], 3(or 17)alpha-hydroxysteroid dehydrogenase [E.C. 1.1.1.209] and their respective products, androsterone (ADT) and epitestosterone (EpiT), in the developmental masculinization of sex behavior. EpiT is generally regarded as a hormonally inactive 17alpha-epimer of testosterone (T). In rats, the kidney is the primary site of EpiT formation, whereas in humans it originates from the gonads, with only a small contribution secreted by the adrenals. Because the ratio of T to EpiT is nearly constant, it is presently used for assessing steroid abuse in competitive sports, where the World Anti-Doping Agency (WADA) considers a T/EpiT ratio >4 evidence of T doping. Despite its central role in the detection of illict anabolic steroid use, our knowledge of factors effecting EpiT production is poor. Clues in the literature, however, reveal that prostaglandin-mediated processes, such as LHRH release, may influence its production. Antimycotics, NSAIDs, and opioid analgesics used in sports medicine are all known to effect prostaglandin E2 synthesis. Primary PGs are potent inhibitors of ADT oxidation, while indomethacin, a prostaglandin blocker, powerfully inhibits 3alpha-HSD reduction and ADT oxidation. This is significant because ADT inhibits the oxidation of EpiT, and may modulate its antiandrogenic and neuroprotective effects. It is hypothesized that the T/EpiT ratio is increased by COX-2 inhibitors and opiod analgesics, and decreased by antimycotics that do not impair testosterone biosynthesis. Given the devastating personal and career consequences that may result from false positive drug tests, substantive research on the effects of PGE2 manipulations on EpiT is warranted.

背景与目标： : Amateau和McCarthy发表在《自然神经科学》 (2004年6月) 上的发现值得注意，因为它暗示了前列腺素在性发育中的作用。然而，有证据表明，在操纵PGE2时，他们在不知不觉中涉及3α-羟基类固醇脱氢酶 [E.C. 1.1.1.50]，3 (或17) α-羟基类固醇脱氢酶 [E.C.1.1.209] 及其各自的产物，雄酮 (ADT) 和表甾酮 (EpiT)，在性行为的发展男性化中。EpiT通常被认为是睾丸激素 (T) 的激素不活跃的17α-epimer。在大鼠中，肾脏是EpiT形成的主要部位，而在人类中，肾脏起源于性腺，肾上腺仅分泌少量。由于T与EpiT的比率几乎是恒定的，因此目前用于评估竞技运动中的类固醇滥用，世界反兴奋剂机构 (WADA) 认为T/EpiT比率> 4是T掺杂的证据。尽管它在检测合成代谢类固醇的使用中起着核心作用，但我们对影响epi产生的因素的了解却很差。然而，文献中的线索表明，前列腺素介导的过程 (例如LHRH释放) 可能会影响其产生。运动医学中使用的抗真菌药，NSAIDs和阿片类镇痛药都可以影响前列腺素E2的合成。初级pg是ADT氧化的有效抑制剂，而前列腺素阻滞剂吲哚美辛则有效抑制3α-hsd还原和ADT氧化。这很重要，因为ADT抑制EpiT的氧化，并可能调节其抗雄激素和神经保护作用。假设COX-2抑制剂和阿片类镇痛药会增加T/EpiT比，而不会损害睾丸激素生物合成的抗真菌药会降低T/EpiT比。鉴于假阳性药物测试可能会导致毁灭性的个人和职业后果，因此有必要对PGE2操作对EpiT的影响进行实质性研究。

BACKGROUND & AIMS: :Rats have an attenuated febrile response to endogenous pyrogen near the term of pregnancy. Given the fundamental role of E-series prostaglandins (PGEs) in mediating the febrile response to blood-borne endogenous pyrogen, the present experiments were carried out to determine whether PGEs increase in the area surrounding the organum vasculosum laminae terminalis (peri-OVLT) of near-term pregnant (P) rats as in nonpregnant (NP) rats after intravenous (iv) administration of recombinant rat interleukin-1beta (rrIL-1beta). Core temperature was measured by telemetry and peri-OVLT interstitial fluid was sampled in 12 NP and 12 P chronically instrumented, Sprague-Dawley rats by microdialysis for determination of total PGEs by radioimmunoassay. Basal core temperatures were higher in NP compared with P rats (NP 37.9 degrees C +/- 0.5, P 36.9 degrees C +/- 0.4; P < 0.05), but basal peri-OVLT PGEs were similar in both groups (NP 260 +/- 153 pg/ml, P 278 +/- 177 pg/ml; P =not significant). Intravenous administration of rrIL-1beta to NP rats produced a significant increase in core temperature with a latency, magnitude, and duration of 10 min, 0.87 degrees C, and at least 170 min, respectively; peri-OVLT PGEs were increased significantly by 30 min and averaged 270% above basal levels throughout the experiment. In P rats, however, neither core temperature nor peri-OVLT PGEs increased significantly after iv administration of rrIL-1beta. Intravenous administration of vehicle did not significantly alter core temperature or peri-OVLT PGEs in either group of rats. Thus peri-OVLT PGEs do not increase in P rats as they do in NP rats after iv administration of rrIL-1beta. The mechanism of this interesting component of the maternal adaptation to pregnancy, which likely plays a major role in mediating the attenuated febrile response to endogenous pyrogen near the term of pregnancy, warrants further investigation.

背景与目标： : 大鼠在怀孕期间对内源性热原的发热反应减弱。鉴于E系列前列腺素 (PGEs) 在介导对血源性内源性热原的发热反应中的基本作用，进行了本实验，以确定在静脉内 (iv) 施用重组大鼠后，近期怀孕 (P) 大鼠的器官脉管终层 (peri-OVLT) 周围区域的PGEs是否增加 (rrIL-1beta)。大鼠interleukin-1beta)。通过遥测法测量核心温度，并通过微透析在12 NP和12 P长期仪器的Sprague-Dawley大鼠中采样周围OVLT间质液，以通过放射免疫测定法测定总PGEs。与P大鼠相比，NP的基础核心温度更高 (NP 37.9 ℃/- 0.5，P 36.9 ℃/- 0.4; P <0.05)，但两组的基础peri-OVLT PGEs相似 (NP 260/- 153 pg/ml，P 278 +/- 177 pg/ml; P = 不显着)。向NP大鼠静脉内施用rrIL-1beta会产生核心温度的显着增加，潜伏期，幅度和持续时间分别为10分钟，0.87摄氏度和至少170分钟; peri-OVLT PGEs显着增加30分钟，并且在整个实验中平均270% 高于基础水平。然而，在P大鼠中，静脉注射rrIL-1beta后，核心温度和周围OVLT PGEs均未显着增加。静脉内施用媒介物不会显着改变两组大鼠的核心温度或周围OVLT PGEs。因此，在iv给药rrIL-1beta后，P大鼠中的peri-OVLT PGEs不会像在NP大鼠中那样增加。孕产妇适应妊娠的这一有趣成分的机制可能在介导妊娠期间对内源性热原的减弱的发热反应中起主要作用，值得进一步研究。

BACKGROUND & AIMS: :Addition of substance P (SP) to astrocytes cultured from rat neonatal spinal cord evoked a time- and concentration-dependent increase in the accumulation of phosphoinositol and the release of prostaglandin (PG) D2 and PGE2. Both basal and stimulated releases were reduced to similar levels by indomethacin. In contrast, astrocytes cultured from cerebral cortex and cerebellum showed no SP-stimulated increase in phosphoinositol accumulation or release of PGs. Release of PGD2 and PGE2 was, however, stimulated by the calcium ionophore A23187, and both phosphoinositol accumulation and PG release were stimulated from cortical astrocytes incubated in the presence of serum. The results from this study suggest that SP-stimulated phosphoinositol accumulation and release of PGs from cultured rat neonatal astrocytes are regionally specialised in favour of cells derived from spinal cord.

背景与目标： : 从大鼠新生脊髓培养的星形胶质细胞中添加p物质 (SP) 引起磷酸肌醇积累和前列腺素 (PG) D2和pge2释放的时间和浓度依赖性增加。消炎痛将基础释放和刺激释放降低到相似的水平。相反，从大脑皮层和小脑培养的星形胶质细胞未显示SP刺激的磷酸肌醇积累或pg释放增加。然而，钙离子载体A23187刺激了PGD2和PGE2的释放，并且在血清存在下孵育的皮质星形胶质细胞刺激了磷酸肌醇的积累和PG的释放。这项研究的结果表明，SP刺激的磷酸肌醇积累和从培养的大鼠新生星形胶质细胞中释放的pg在区域上是专门的，有利于脊髓来源的细胞。

BACKGROUND & AIMS: :We examined the relative contribution of endothelial and vascular smooth muscle-derived prostaglandins and endothelium-derived relaxing factor in modulating both the large coronary artery and resistance vessel responses to thromboxane in vivo. Vascular responses to the thromboxane analogue U46619 were measured in four separate experimental protocols: 1) The vascular responses were measured in the presence and absence of intact endothelium to examine the role of endothelium-derived vasodilators. 2) Responses were measured in the presence of intact endothelium before and after inhibition of cyclooxygenase with indomethacin to examine the role of endothelial and vascular smooth muscle-derived prostaglandins. 3) Responses were measured after endothelial removal before and after indomethacin to examine the role of vascular smooth muscle-derived prostaglandins. 4) Responses were measured after indomethacin and before and after removal of endothelium to examine the role of endothelium-derived relaxing factor. In anesthetized dogs (n = 41) that underwent constant pressure perfusion of the left anterior descending coronary artery (LAD), LAD diameter was measured with sonomicrometer crystals, and coronary flow was measured with an electromagnetic flow probe. Intracoronary infusion of U46619 (0.01-1.0 microgram/min) produced a dose-dependent constriction of LAD. Constriction of the LAD was augmented after endothelial removal, after indomethacin treatment in both the presence and absence of endothelium, and after removal of the endothelium in the presence of indomethacin. Inhibition of prostaglandin synthesis had the greatest effect of augmenting constriction of LAD to thromboxane. Coronary flow was decreased by U46619 only in the presence of indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： : 我们检查了内皮和血管平滑肌衍生的前列腺素和内皮衍生的舒张因子在体内调节大冠状动脉和阻力血管对血栓烷的反应中的相对贡献。在四个独立的实验方案中测量了对血栓素类似物U46619的血管反应: 1) 在存在和不存在完整内皮的情况下测量血管反应，以检查内皮衍生的血管扩张剂的作用。2) 在吲哚美辛抑制环氧合酶之前和之后，在完整的内皮存在下测量反应，以检查内皮和血管平滑肌衍生的前列腺素的作用。3) 在吲哚美辛前后测量内皮去除后的反应，以检查血管平滑肌衍生的前列腺素的作用。4) 在吲哚美辛之后以及去除内皮之前和之后测量反应，以检查内皮衍生的松弛因子的作用。在接受左前降支冠状动脉 (LAD) 恒压灌注的麻醉犬 (n = 41) 中，用sonomicrometer晶体测量LAD直径，并用电磁流量探针测量冠状动脉流量。冠状动脉内输注U46619 (0.01-1.0微克/分钟) 产生LAD的剂量依赖性收缩。内皮去除后，在存在和不存在内皮的情况下进行吲哚美辛处理后，以及在存在吲哚美辛的情况下去除内皮后，LAD的收缩增加。抑制前列腺素的合成具有最大的作用，可以增加LAD对血栓烷的收缩。只有在吲哚美辛存在的情况下，U46619才能减少冠状动脉血流。(摘要截短于250字)

BACKGROUND & AIMS: :Prostaglandins (PGs) are a family of lipid compounds that are derived from arachidonic acid via the cyclooxygenase pathway, and consist of PGD2, PGI2, PGE2, PGF2, and thromboxane B2. PGs signal through G-protein coupled receptors, and individual PGs affect allergic inflammation through different mechanisms according to the receptors with which they are associated. In this review article, we have focused on the metabolism of the cyclooxygenase pathway, and the distinct biological effect of each PG type on various cell types involved in allergic airway diseases, including asthma, allergic rhinitis, nasal polyposis, and aspirin-exacerbated respiratory disease.

背景与目标： : 前列腺素 (PGs) 是一类脂质化合物，通过环氧合酶途径衍生自花生四烯酸，由PGD2，PGI2，PGE2，PGF2和血栓烷b2组成。PGs通过g蛋白偶联受体发出信号，单个PGs根据与其相关的受体通过不同机制影响过敏性炎症。在这篇综述文章中，我们重点关注环氧合酶途径的代谢，以及每种PG类型对涉及过敏性气道疾病的各种细胞类型 (包括哮喘，过敏性鼻炎，鼻息肉病和阿司匹林加剧的呼吸道疾病) 的独特生物学作用。

BACKGROUND & AIMS: AIM:The effects of losartan on blood pressure and on renal function have mainly been attributed to AT1 receptor blockade. Experimental evidence suggests that these effects could also be related to the actions of angiotensin II through AT2 receptors or to vasodilatory systems. The present study was therefore designed to investigate the manner in which the acute effects of losartan on renal excretory function are affected during simultaneous administration of an AT2 receptor antagonist, a kinin B2 receptor antagonist, a cyclo-oxygenase inhibitor or a nitric oxide synthesis inhibitor.

MATERIALS AND METHODS:The AT2 receptor antagonist PD 123319 (10 mg/kg), the bradykinin B2 receptor antagonist Hoe 140 (30 mu g/kg), the cyclo-oxygenase inhibitor meclofenamate (5 mg/kg) and the nitric oxide synthesis inhibitor NG-monomethyl-L-arginine (1 mu g/kg per min) were administered separately with acute intravenous losartan (1 mg/kg) to spontaneously hypertensive rats and the effects on mean arterial pressure and renal excretory function were assessed.

RESULTS:Losartan reduced mean arterial pressure by 11.1 +/- 5.7 mmHg and increased the glomerular filtration rate, urine flow and sodium excretion rate. The decrease in mean arterial pressure was blocked in the presence of NG-monomethyl-L-arginine but not during concurrent administration of PD 123319, Hoe 140 or meclofenamate. The increase in glomerular filtration rate induced by losartan was blunted by Hoe 140, meclofenamate and NG-monomethyl-L-arginine. Co-administration of PD 123319, Hoe 140 or meclofenamate, but not of NG-monomethyl-L-arginine, partially blunted the diuresis and natriuresis induced by losartan.

CONCLUSIONS:Nitric oxide participates in the antihypertensive action of losartan. Kinins, prostaglandins and nitric oxide appear to be involved in the effects of losartan on the glomerular filtration rate. The increases in urine flow and sodium excretion rate induced by losartan depend partially on AT2 receptors, kinins and prostaglandins.

背景与目标： 目的 : 氯沙坦对血压和肾功能的影响主要归因于AT1受体阻滞。实验证据表明，这些作用也可能与血管紧张素II通过AT2受体的作用或血管舒张系统有关。因此，本研究旨在研究在同时施用AT2受体拮抗剂 (激肽B2受体拮抗剂) 期间影响氯沙坦对肾脏排泄功能的急性作用的方式，环加氧酶抑制剂或一氧化氮合成抑制剂。材料和方法: AT2受体拮抗剂PD 123319 (10 mg/kg)，缓激肽B2受体拮抗剂Hoe 140 (30 μ g/kg)，将环加氧酶抑制剂甲氯芬那酯 (5 mg/kg) 和一氧化氮合成抑制剂NG-单甲基-L-精氨酸 (1 μ g/kg/min) 与急性静脉氯沙坦 (1 mg/kg) 分别给予自发性高血压大鼠，并评估了对平均动脉压和肾脏排泄功能的影响。
结果 : 氯沙坦可使平均动脉压降低11.1/- 5.7 mmHg，并增加肾小球滤过率，尿液流量和钠排泄率。在存在NG-单甲基-L-精氨酸的情况下，平均动脉压的降低被阻断，但在同时施用PD 123319，Hoe 140或甲氯芬酯期间不被阻断。氯沙坦引起的肾小球滤过率的增加被140，甲氯芬酯和NG-单甲基-L-精氨酸抑制。同时使用PD 123319，Hoe 140或甲氯芬那酯，但不使用NG-单甲基-L-精氨酸，部分减弱了氯沙坦诱导的利尿和利尿。
结论 : 一氧化氮参与氯沙坦的降压作用。激肽，前列腺素和一氧化氮似乎与氯沙坦对肾小球滤过率的影响有关。氯沙坦诱导的尿液流量和钠排泄率的增加部分取决于AT2受体，激肽和前列腺素。