Abortion-inducing effect of prostaglandin F2-alpha in the mid-trimester of pregnancy

Prostaglandin (PG) F2-alpha was administered extraamnially to 70, and intraammially to 51 pregnant women to induce abortion in the 14th to 28th weeks of pregnancy. With intraamnial infusion of PGF2-alpha (25 mg/8-12 hours), the mean induction time was 27.1 hours and thus, oxytocin, too, was required in 19.6% of the cases. With extraamnial infusion of 5 mg PGF2-alpha at 4 to 6 hour intervals, mean induction time was 34.0 hours and addition of oxytocin was required in 46.1% of the cases. Moreover, if 15 to 30 mg of PGF2-alpha was infused at 18 to 29 hour intervals, or 1 mg at 2 hour intervals, the induction of abortion was considerably prolonged. In primigravidae, or in the 14th to 18th weeks pregnancy, the abortive effect of PGF2-alpha was weaker than in multigravidae or in the 19th to 28th weeks of pregnancy. In the case of intrauterine fetal deaths, the abortive effects was more marked than in intact pregnancies. After extraamnial infusion of PGF2-alpha, the uterine contractions were less coordinated than after intraamnial dosage. In about one-third of abortion induced by extraamnial PGF2-alpha, the fetal heart was found to work for 5 to 15 minutes after abortion.     

The mode of action of prostaglandin E2, F2 alpha and prostacyclin on vesicourethral smooth muscle

Interactions of prostaglandin E2 (PGE2), F2 alpha (PGF2 alpha) and prostacyclin (PGI2) with Ca2+ on the isometric contraction of rabbit detrusor muscle strips were studied using two types of Ca2+ antagonists of different mechanisms of action: verapamil and sodium nitroprusside (NP). The effects of PGI2 on vesicourethral smooth muscle and their relationship with cholinergic, adrenergic receptors and nervous activity were also investigated. PGE2 and F2 alpha (3 X 10(-8) to 3 X 10(-5) M) caused dose-dependent contraction of the strips. Pretreatment of the strips with verapamil (10(-7) to 10(-5)M) significantly inhibited PGs-induced contraction in a dose-dependent manner, whereas NP(10(-7) to 10(-5)M) failed to suppress the contraction. Relaxation of the preparations once contracted by PGE2 and F2 alpha (3 X 10(-6)M) was induced completely by addition of verapamil (10(-5)M), and incompletely by NP(10(-5) to 10(-3)M). Washing of the strips with Ca2+-free solution containing 0.01 mM EGTA completely eliminated spontaneous activity and diminished basal tension, but replenishment of Ca2+ (0.5 to 10 mM) to the medium caused dose-related contraction and spontaneous activity of the strips. Addition of PGE2 and F2 alpha to the Ca2+-free medium enhanced Ca2+-induced contraction and spontaneous activity during Ca2+ replenishment, which were significantly inhibited by pretreatment with verapamil (10(-7) to 10(-5)M) in a dose-dependent manner, but not affected by NP (10(-7) to 10(-5)M). In Ca2+-free medium containing 0.1 mM EGTA, PGE2 and F2 alpha caused a slight degree of tension increase of the strips dose-dependently at the higher concentration exceeding 3 X 10(-6)M. PGI2 (10(-9) to 3 X 10(-4)M) caused dose-dependent contraction of the strips from the bladder body, base and the urethra. The contractile action of PGI2 was greatest on the bladder body, less on the base and minimal on the urethra. The effect of PGI2 was less potent than those of PGE2 and F2 alpha. The PGI2-induced contraction was slow in onset, short lasting, and not affected by pretreatment with phentolamine, propranolol, atropine, hexamethonium, hemicholinium-3 and tetrodotoxin. The interactions of PGI2 with Ca2+ were similar to those of PGE2 and F2 alpha.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prostaglandin F2-alpha bladder irrigation for control of intractable cyclophosphamide-induced hemorrhagic cystitis

We report a case of intractable cyclophosphamide-induced hemorrhagic cystitis. Conservative therapy, including suprapubic cystostomy with through-and-through bladder irrigation, failed to slow the bleeding. We then instilled 200 cc of a 0.7 mg. per cent solution of prostaglandin F2-alpha into the bladder for 4 hours daily. The bleeding ceased completely by the end of treatment 5 and the patient remains free of hematuria. There were no side effects noted during the 5 days of treatment. This form of therapy offers an effective, safe and easy alternative to more caustic bladder irrigants and methods of treatment.     

The influence of some synthetic prostaglandin F2alpha analogous on rat lung

The role of prostaglandins and their synthetic analogous at the level of the female genital system is multiple. The synthetic analogous of the prostaglandin F2 alpha are utilised in a large area of treatments, for multiple purposes, but their influence on the lung is not so well known. The study was made on 2 lots with 12 non pregnant female rats: the first lot was the witness lot and didn't receive any substance. The second lot received 25 micrograms/kg/day Flavoliz (synthetic analogous of the prostaglandin F2 alpha). The prostaglandinic analogous produces vasodilating effects on the lung blood vessels and moderate pulmonary destruction.     

Spasmogenic qualities of prostaglandin F2alpha in the cat.

Available data indicate that the concentration of prostaglandin F2alpha required to produce arterial spasm in an experimental model is approximately a thousand-fold higher than the concentration that occurs under physiological conditions. The spasmogenic platelet factor which has been previously described is shown to be a substance other than prostaglandin F2alpha because of differences in susceptibility of the two substances to enzymatic digestion.     

Effect of site of stimulation on the guinea pig's electrically evoked brain stem response

Stimulation by a bipolar modiolus electrode yields a wider dynamic range than does monopolar stimulation at the same site. Stimulation via a single electrode in the scala tympani or scala vestibuli is characterized by a precipitous input-output function, but current passing from one scala to the other generates a discontinuous function with a shallow slope at low intensities and a steep slope at high intensities.     

The effect of prostaglandin F2 alpha on the gastrointestinal movement after urological surgery

To facilitate postoperative flatus, Prostaglandin F2 alpha (PGF2 alpha) was given intravenously to 23 patients who underwent urological operations. The patients were 14 males and 6 females aged from 20 to 77 years old. Patients with hypertension or cardiovascular disease were not included. Twelve operations were performed under general anesthesia, and 8 under epidural anesthesia. Thirteen operations were performed for the upper urinary tract or adrenal gland, and 5 were for the lower urinary tract. In 2 cases, the peritoneal cavity was opened and operations were performed on the intestines. PGF2 alpha 2000 micrograms was added to the postoperative drip infusion and administered in 2 to 3 hours. Until the first flatus was recognized, PGF2 alpha was given once a day in the same manner. Twenty-six patients, 10 of whom were given either vagostigmine or pantothen postoperatively, served as the control group. PGF2 alpha accelerated the postoperative flatus by 8.7 hours (mean) compared with the control group, but it was not significant. The onset of flatus was significantly promoted under epidural anesthesia. Gastrointestinal movement tended to be facilitated in the PGF2 alpha group after lower urinary tract surgery and in the patients over 50 years old. Three patients complained of severe abdominal pain as a side effect; and, injection of PGF2 alpha was stopped. In 7 patients, mild stomachache , vascular pain, nausea, vomiting or elevation of blood pressure were observed.     

The use of prostaglandin F2 alpha for the prophylaxis of cyclophosphamide induced cystitis in rats

It is well-established that cystitis is a significant cause of morbidity after cyclophosphamide administration in clinical populations. We induced hemorrhagic cystitis in rats using cyclophosphamide and compared controls to those pretreated with prostaglandin F2 alpha. Rats were then evaluated for differences in bladder weights, gross edema, gross bleeding, and histologic changes. The weights of the bladders which had been treated with cyclophosphamide were 94% greater than the controls. The weights of the bladders which were pretreated with prostaglandin F2 alpha before cyclophosphamide were only 19% greater than controls. Significant differences were found between cyclophosphamide controls and prostaglandin F2 alpha pretreated groups for gross weight (p less than .0005), gross edema (p less than .0005), and histology (.0005 less than p less than .005). We conclude that prostaglandin F2 alpha may be helpful in preventing cyclophosphamide induced cystitis.     

Immunohistochemical localization of prostaglandin F2 alpha in reperfused gerbil brain.

Immunohistochemical localization of prostaglandin (PG) F2 alpha synthesized during recirculation following experimental forebrain ischemia was studied in Mongolian gerbils. The bilateral carotid arteries were clamped for 5 minutes, and the brains were frozen in situ after 5 minutes of recirculation. Sham-operated gerbils not subjected to arterial occlusion served as controls. Cryostat sections containing dorsal hippocampus 10 microns in thickness were incubated in rabbit anti-PGF2 alpha serum and stained with avidin-biotin-peroxidase complex after fixation in carbodi-imide and Zamboni's solution. In specimens from control animals, blood vessels were faintly stained with anti-PGF2 alpha serum, while neurons and glial cells were less intensely stained or unstained. Specimens from reperfused gerbils demonstrated strongly positive staining for PGF2 alpha in blood vessels, neurons (especially hippocampal pyramidal neurons), and glial cells. Staining for PGF2 alpha in the reperfused animals was substantially diminished by pretreatment with indomethacin (10 mg/kg, i.p.). The results indicate that recirculation after forebrain ischemia results in an increase in PGF2 alpha in neurons, glial cells, and blood vessels.     

The action potential of guinea pig bladder smooth muscle

The smooth muscle of the guinea pig bladder demonstrates in vitro spontaneous electrical activity in the form of action potentials which are associated with contraction. The action potential frequency is highly voltage-sensitive. The relative contributions of Na, Ca and K to the action potential elicited by depolarizing current have been studied using intracellular microelectrodes. In solutions in which NaCl is replaced by sucrose, the membrane hyperpolarizes and the rate of rise and after-hyperpolarization of the elicited action potential is increased. The amplitude is unaffected. In Ca-deficient solutions, the membrane depolarizes, the rate of rise and amplitude of the action potential is reduced, and the after-hyperpolarization is decreased. Nifedipine reduces amplitude and rate of rise but does not affect after-hyperpolarization. In the presence of the K-channel antagonist TEA, the duration of the action potential is prolonged, but the amplitude and rate of rise are unaffected. After-hyperpolarization is not reduced. It is concluded that the action potential of guinea pig bladder muscle, like many other smooth muscles studied, is Ca-based. Repolarization depends on changes in K conductance. The after-hyperpolarization is voltage-sensitive.     

Endogenous prostaglandin F2 alpha in the hyperdynamic state of severe sepsis in man

Nine surgical patients underwent haemodynamic and respiratory monitoring during the course of severe sepsis. Endogenous PGF2 alpha levels in mixed venous and arterial plasma were measured. Results indicate pulmonary net release of PGF2 alpha, since arterial levels (1252 +/- 119 pg/ml) are significantly higher than mixed venous ones (824 +/- 89 pg/ml) in full-pronounced hyperdynamic septic shock. By contrast, the inactive metabolite KH2PGF2 alpha was found in lowest concentrations during shock (368 +/- 72 pg/ml) which suggests impaired pulmonary degradation. It is concluded that circulating PGF2 alpha is a marker of stimulated prostaglandin production in severe human sepsis.     

The role of some prostaglandin analogues in experimental intoxication produced by carbon tetrachloride in rats

Prostaglandins are synthesized ubiquitously in the body from unsaturated fatty acids and they act as paracrine messengers. We have studied the influence of a prostaglandin analogue on experimental induced hepatopathy. The tested compound is a synthetic isopropyl ester of PGF2 alpha (IPEF) and as hepato-toxic agent we used CCl4. We worked on four groups of 4 adult male rats each. Group I received no substance; Group II received CCl4 0.1 ml/bw/per os, single dose, for three days; Group III received CCl4 as series I and IPEF 15 micrograms/bw i.p., single dose daily, one hour before CCl4 administration; Group IV received CCl4 as series I and IPEF 50 micrograms/bw i.p., single dose daily. Twenty-four hours after the last administration, samples of blood were taken and ALT, AST, LDH as well as conjugate and unconjugate bilirubin were determined. We also determined MDH, GSH and glutathion peroxidase, in liver homogenate. Our data show that MDH levels are increased in Group I (20.81 +/- 3.15 microM/microgram protein) as compared with both Group III (8.44 +/- 1.32 microM/microgram protein) and IV (7.31 +/- 1.92 microM/microgram protein) which might suggest that prostaglandin analogue IPEF decreases the polyunsaturated fatty acids degradation, at both low and high level. ALAT levels for group that received CCl4 (782 +/- 20.8 U/L) are significantly higher than those for group III (264 +/- 15.4 U/L) and IV (227 +/- 8.4 U/L) which received IPEF at low, respectively high dose. Our data suggest that the synthetic prostaglandin analogue presents stabilizing membrane effects (plasmatic and membrane of some cellular organelles) and reduces peroxide radicals production.     

The effectiveness of angiotensin II antagonist on experimental pulmonary embolism--comparison of propranolol with prostaglandin F2 alpha

We studied the effects of angiotensin II (A-II) antagonist, propranolol and prostaglandin F2 alpha (PGF2 alpha) on arterial hypoxemia after injecting autologous muscle to induce massive pulmonary embolism. Twenty-four anesthetized paralyzed dogs were divided into four groups; control, intravenous A-II antagonist (1-sarcosine, 8-isoleucine A-II) infusion at 5 micrograms.kg-1.min-1, intravenous propranolol injection at 1.5-2.0 mg, and intravenous PGF2 alpha infusion at 1 microgram.kg-1.min-1. With FIO2 of 0.33, the administration of A-II antagonist produced an increase in arterial PO2 from 134 +/- 16 (mean +/- SE) to 155 +/- 11 mmHg during infusion, and to 160 +/- 9 mmHg 30 min after infusion. Simultaneous hemodynamic measurements demonstrated no significant changes in arterial blood pressure and heart rate, but a slight increase in cardiac output was observed. On the other hand, propranolol and PGF2 alpha did not reverse the pulmonary oxygenation. Cardiac output decreased after propranolol, and alveolar dead space and pulmonary artery pressure increased further after PGF2 alpha. We conclude that A-II antagonist may be effective in the treatment of massive pulmonary embolism, possibly by improving the ventilation-perfusion relationship. The exact mechanism of the effect of A-II antagonist has not been clarified.     

大鼠骨髓干细胞种植于豚鼠脱细胞动脉移植后局部IgG和补体C3沉积研究

目的 探讨大鼠骨髓干细胞种植于豚鼠脱细胞血管支架方法构建组织工程血管的免疫原性.方法 选取健康纯系雄性SD大鼠80只,体质量200 ～ 250 g,随机分为4组,皮下包埋不同移植物:骨髓干细胞种植组(A组,种植大鼠骨髓干细胞的脱细胞豚鼠血管,n =20)、单纯脱细胞组(B组,单纯脱细胞的豚鼠血管,n=20)、新鲜异种血管组(C组,新鲜豚鼠血管,n=20)、假手术组(D组,不包埋任何标本,n=20).术后第3、7、15、30、60天每组处死4只大鼠,获取大鼠血清并取出移植物.苏木素-伊红(HE)染色观察豚鼠血管脱细胞处理效果及移植物表面炎性反应强度,免疫组织化学方法检测移植物表面抗豚鼠血管IgG和补体C3沉积.结果 (1)HE染色显示每组移植物中均可见明显炎性细胞浸润,A组及B组的炎症浸润程度明显低于C组.(2)免疫组织化学法检测:各组移植物表面有明显的抗豚鼠血管IgG沉积.术后3d各组平均吸光度(IA)值差异无统计学意义(A组0.1506 ±0.0394,B组0.1632±0.0340,C组0.1668±0.0510,P＞0.05).术后7、15、30、60dC组平均IA值(0.2157±0.0452、0.2563±0.0442、0.2752±0.0579、0.2545 ±0.0466)高于A组(0.1633±0.0388、0.1787±0.0532、0.1692±0.0406、0.1633±0.0282)、B组(0.1555±0.0348、0.1740±0.0364、0.1698±0.0330、0.1621±0.0349,P＜0.05).术后各时间点A组较B组均差异无统计学意义(P＞0.05).(3)免疫组织化学法检测显示移植物表面有明显的大鼠补体C3沉积.术后3、7、15 d各组平均IA值差异无统计学意义(A组0.1304±0.0313、0.1552±0.0425;B组0.1316±0.0254、0.1535±0.0396;C组0.1671±0.0422、0.1766±0.0493,P＞ 0.05).术后30、60dC组平均IA值(0.2401±0.0706、0.2674±0.0788、0.2044±0.0494)高于A组(0.1612±0.0358、0.1597±0.0439、0.1382±0.0299)、B组(0.1603±0.0591、0.1517±0.0404、0.1407±0.0288,P＜0.05).术后各时间点A组较B组差异无统计学意义(P＞0.05).结论 骨髓干细胞种植组织工程血管及脱细胞处理血管的免疫排斥反应强度明显低于新鲜异种血管;同种骨髓干细胞种植于异种脱细胞血管支架方法构建的组织工程血管,具有较低的免疫原性.     

Urinary excretion and glomerular synthesis of prostaglandin E2 and prostaglandin F2 alpha in cirrhotic, non-ascitic rats: the effects of sodium overload

The urinary excretion of aldosterone, kallikrein and prostaglandin E2 (PGE2) was studied in sodium-retaining (RC) and nonretaining (NRC), nonascitic cirrhotic rats, under basal conditions and after an oral sodium load (5 mmol). The glomerular synthesis of PGE2 was measured in RC rats under the same conditions. Both groups of cirrhotic animals showed a decreased urinary excretion of PGE2. Isolated glomeruli of RC rats produced less PGE2 than those of the control animals, both under basal conditions and after the sodium load. The NRC group was the only one able to increase the urinary excretion of kallikrein in response to the sodium load. These findings could contribute to explain the early physiopathological events of hepatic cirrhosis.