Prostaglandin E1, E2 and oxytocin in labor induction

The risks of induction must be carefully weighed against the risks of allowing the pregnancy to continue and not inducing labor. The aim of the study was to show labor and neonatal outcome of 335 deliveries inducted in 2004 at Institute of gynecology and obstetrics Clinical Center of Serbia. Inductions were performed with PGE2, PGE1 and Oxytocin. The best ripening effect was noted in PGE2 group. The average duration of labor was 8.6h in PGE1group, 5.9h in PGE2 group and 10.4h in OT group. Sixty eight labors finished with cesarean section (20%). Comparing duration of labor, percentage of emergency cesarean sections, incidence of fetal distress during the labor we suggest Dinoprostone, placed intracervically, as an agent of choice for induction of labor.     

The effect of indomethacin and metamizole on ureteral motility and urine flow in sheep

Summary The objective of this study was to evaluate the effect of two non-steroid anti-inflammatory drugs, indomethacin and metamizole, on ureteral peristalsis during acute occlusion similar to the situation in renal colic. In 12 pentobarbital anesthetized sheep, both ureters were cannulated and the frequency of ureteral contractions, urine flow, mean ureteral pressure and blood pressure were recorded during 10-min control and i.v. drug administration periods. Both indomethacin (1–2 mg/kg) and metamizole (60–120 mg/kg) showed a dose dependent reduction in peristaltic frequency without reduction of the mean pressure. In addition, the pressure amplitude of the peristaltic waves was also lowered, particularly with indomethacin. Only indomethacin reduced the urine flow. Arterial blood pressure was elevated by both drugs, particularly after the first dose of indomethacin. It can be concluded that indomethacin and metamizole reduce ureteral peristaltic frequency, probably blocking the impulse transmission at the ureteropelvic junction.For the partial fulfillment of a Master's degree in Pharmacology     

胃粘膜上皮“适应性细胞保护”机制防止胃肿瘤发生的作用

投用致癌剂的对照组其胃肿瘤发生率为22.2％。若同时给予40％Z醇液空腹灌胃,则胃肿瘤发生率达55.9％。如在给乙醇液前15分钟,先给予4％的辣椒煎液灌胃,则胃肿瘤发生率只有20.0％,相近于对照组的水平(后2组差别有极显著意义,P<0.01)。这种给损伤剂(乙醇)之前先给予微刺激剂(辣椒)所产生的胃粘膜的保护作用,是通过促使胃粘膜上皮细胞合成内源性前列腺素(PGs)来实现的,是一种“适应性细胞保护”机制。这种保护胃粘膜的作用可降低胃肿瘤的发生率。     

前列腺液中尿酸引起ⅢB前列腺炎84例报告

目的 :探讨前列腺液 (EPS)中尿酸 (UA)与前列腺素E2 (PGE2 )浓度与慢性盆痛症状之间的相互关系 ,以及UA引发ⅢB前列腺炎的可能机制。方法 :按国际慢性前列腺炎分类诊断标准诊断 ,将 84例慢性前列腺炎患者分为两组 ,即ⅢA组 39例 ;ⅢB组 4 5例 ;正常对照 (对照组 ) 13例。分别进行国际前列腺炎症状评分 (CP SI)和检测EPS中白细胞数、pH值、UA和PGE2 浓度。结果 :①ⅢB组患者慢性盆痛症状评分 (CPSI P)高于ⅢA组 ,EPS中UA浓度高于ⅢA组和正常对照组 ,pH值低于ⅢA和正常对照组 ,均差异有显著性意义 (均 P <0 .0 5 )。②ⅢB组和ⅢA组的PGE2 平均浓度高于正常对照组 ,差异有显著性意义 (P <0 .0 5 ) ,但是ⅢA组和ⅢB组间差异无显著性意义 (P >0 .0 5 )。CPSI P与EPS中的UA ,PGE2 之间存在正相关 (P <0 .0 1)。结论 :ⅢB组患者EPS中高浓度的UA激活环氧化酶 ,使局部的PGE2 升高 ,从而引起慢性盆痛症状 ,其严重程度与EPS中的UA、PGE2 浓度呈正比。同时PGE2 又使UA更容易渗入EPS ,形成UA和PGE2 之间的恶性循环 ,使ⅢB前列腺炎迁延不愈。     

Prostaglandins and CGRP release from cardiac sensory nerves

Summary (1) The possible influence of Prostaglandins (PG) E₁ and I₂ as well as ischaemia, ouabain and bradykinin on the outflow of calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity (LI) from the guinea-pig heart was studied in vitro. (2) Exposure to PGE₁ (10^–5 M), but not PGI₂ (10^–5 M), induced an increased outflow, suggesting release of CGRP-LI. PGE₁ simultaneously increased the contractile force and heart rate while no effects were observed on perfusate volume or outflow of NPY-LI. PGI₂ had no effect on contractile parameters or coronary flow. In separate experiments on capsaicin-pretreated animals, the stimulatory effects of PGE₁ on heart rate and contractile force remained unchanged while no increased CGRP-LI outflow was detectable. (3) Ouabain, bradykinin and reperfusion after total stop-flow ischaemia was associated with an indomethacin-resistant increase in perfusate levels of CGRP-LI but not of NPY-LI. While ouabain markedly increased the contractile force, exposure to bradykinin or ischaemia did not induce any clear-cut changes in contractile force or heart rate. (4) Capsaicin-exposure evoked a markedly increased outflow of CGRP-LI but not of NPY-LI in combination with an increase in heart rate and a decrease in contractile force. Repeated administration of capsaicin induced tachyphylaxis. The stimulatory effects of capsaicin on CGRP-LI outflow and heart rate, but not the negative inotropic effect, did not occur in capsaicin-pretreated animals. (5) It is concluded that PGE₁, but not PGI₂, can activate cardiac capsaicin-sensitive fibres as revealed by increased outflow of CGRP-LI. The cardiostimulatory effects induced by PGE₁ are not related to CGRP release, however. A possible prostaglandin link in the CGRP-LI released by ouabain, bradykinin or ischaemia seems unlikely. Send offprint requests to: A. Franco-Cereceda at the above address     

鸡矢藤提取物对小白鼠离体子宫的作用

鸡矢藤[Paederia Scandens]提取物0.32mg 加入营养槽内,对小白鼠各期离体子宫的收缩张力、收缩强度、收缩频率以及子宫活动力均有增强作用。与给药前比较,诱导期组分别增加85%、47%、21%和72%;动情期组分别增加70%、77%、41%和41%;非动情组分别增加47%、76%、62%和66%,而且三组间作用无显著性差异。本品还能增强 PGE_2对小白鼠离体子宫的收缩张力、收缩强度、收缩频率以及子宫活动力。与 PGE_2的作用比较,分别增加34%、39%、9%和45%,但收缩频率增加无统计学意义(P>0.05)。上述结果表明,鸡矢藤提取物对小鼠子宫有显著性兴奋作用,而且还能增强PGE_2对小鼠子宫兴奋作用,其机制尚待进一步研究。     

The therapeutic value of vasodilator prostaglandins in multiple organ failure associated with sepsis

There is considerable evidence from animal and human studies of sepsis and acute lung injury that prostacyclin and PGE₁ may have a beneficial effect on tissue perfusion with a reduction in the severity of tissue damage associated with these disorders. As yet, there are no good data from controlled clinical trials that these agents improve survival and it is not clear whether in the future such data will be forthcoming. Nevertheless, using various physiological end-points, both prostaglandins seem to be beneficial in sepsis and when used in combination with the whole process of Intensive Therapy, may contribute to the survival of some cases. Although the assessment of combinations of agents designed to inhibit mediator release might be more useful, it remains to be seen whether the relatively insensitive controlled clinical trial, with survival as its endpoint, is the appropriate tool for assessing efficacy in the ITU. Perhaps, the consensus approach has something to offer in this situation!     

Biocompatibility of Hemoglobin Solutions. I. Reactions of Vascular Endothelial Cells to Pure and Impure Hemoglobins

Hemoglobin (Hb) solutions can cause vasoconstriction and activation of intravascular coagulation. Because the endothelium plays a major role in the regulation of vascular tone and hemostasis, a study was conducted of human umbilical vein endothelial cells (EC) incubated with various Hbs. Cell injury was evaluated by electron microscopy and the release of lactic dehydrogenase, H2O2, and procoagulant "tissue factor." Cell reaction was assessed by the measurement of 6-keto-prostaglandin F (PGF)1 alpha (metabolite of prostacyclin) and thromboxane B2 (metabolite of thromboxane A2). Incubation with unmodified bovine hemoglobin for 24 h caused no cell injury and a reaction characterized by 48.4 +/- 8.2% increase in 6-keto-PGF1 alpha production, accompanied by 40.2 +/- 9.4% reduction in thromboxane (Tx)B2 (compared with a control group of EC incubated with saline solution). Incubation with a nonpure Hb solution (Hb plus red blood cell membrane aminophospholipids; a-PLs) caused cell injury with significant release of tissue factor, plus a reaction characterized by 97.5 +/- 12.5% increase in TxB2 production accompanied by 25.3 +/- 3% reduction in 6-keto-PGF1 alpha. A second nonpure Hb [Hb plus bacterial environmental endotoxin (E)] caused cell injury, the release of tissue factor, and increased production of both prostaglandins, with greater release of TxB2 (197 +/- 17%) than of 6-keto-PGF1 alpha (112 +/- 8.3%). These data indicate that the endothelium reacts differently to pure and nonpure hemoglobins. The biocompatibility of Hb solutions, with regard to vasoconstriction and activation of intravascular coagulation, depends on the absence of stromal a-PLs and bacterial E.     

The effects of ambient and hypothalamic temperatures on the hyperthermic responses to prostaglandins E1 and E2

Summary The effects of ambient and hypothalamic temperatures were studied on the hyperthermic responses to prostaglandins E₁ and E₂ (PGE₁ and PGE₂) injected intraventricularly in the unanesthetized rabbit. Hyperthermic responses to PGE₁ observed at different thermal environments were approximately equal in magnitude and time course. However, the prevailing ambient temperature influenced the thermoregulatory mechanisms by which the hyperthermia was achieved. In a hot environment, PGE₁-hyperthermia was brought about by suppression of heat loss mechanism with little change in heat production. During cold exposure body temperature was raised mainly by an increase in heat production without a significant change in heat loss. PGEs-hyperthermias were attenuated by warming and enhanced by cooling the anterior hypothalamus. These changes in the hyperthermic responses to PGE₁ and PGE₂ are in contrast to those obtained with intraventricular injection of noradrenaline at different ambient temperatures and during hypothalamic heating and cooling. It is therefore unlikely that noradrenaline is involved in the hyperthermic responses to PGEs. On the other hand, the results support the view that prostaglandins may be mediators of pyrogen-induced fever.     

Human multiple myeloma cells express peroxisome proliferator-activated receptor gamma and undergo apoptosis upon exposure to PPARgamma ligands

Multiple myeloma is essentially an incurable malignancy and it is therefore of great interest to develop new therapeutic approaches. We previously reported that human B cell-lymphomas express the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) and are killed by PPARgamma ligands. Herein, we investigate the therapeutic potential of PPARgamma ligands for multiple myeloma. The human multiple myeloma cell lines ANBL6 and 8226 express PPARgamma mRNA and protein. The PPARgamma ligands, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) and ciglitazone, induced multiple myeloma cell apoptosis as determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, loss of mitochondrial membrane potential, and caspase activation. Importantly, the ability of PPARgamma ligands to kill both multiple myeloma cell lines was not abrogated by Interleukin-6 (IL-6), a multiple myeloma growth survival factor. Finally, the RXR ligand 9-cis retinoic acid (9-cis RA) in combination with PPARgamma ligands greatly enhanced multiple myeloma cell killing. These new findings support that PPARgamma ligands may represent a novel therapy for multiple myeloma.