6-keto prostaglandin F1 alpha and thromboxane B2 in isolated, buffer-perfused lungs from monocrotaline pyrrole-treated rats

Monocrotaline pyrrole (MCTP) causes pulmonary endothelial cell injury and pulmonary hypertension in rats. Damage to endothelial cells in culture has been associated with altered prostacyclin (PGI2) production; therefore, it was of interest to determine if MCTP affected pulmonary PGI2 production. Release of the stable metabolites of PGI2 and thromboxane A2, 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) and thromboxane B2 (TxB2), respectively, was examined in isolated, buffer-perfused lungs from MCTP-treated rats at times when elevated pulmonary arterial pressure is first observed (day 7) and when the pulmonary hypertensive state has existed for some time (day 14), 6-keto PGF1 alpha release was not affected by MCTP treatment 7 or 14 days after a single intravenous injection of MCTP. TxB2 release was also unaffected at day 7, however 14 days after treatment TxB2 release was greater in lungs from MCTP-treated rats compared to controls. The concentration of both 6-keto PGF1 alpha and TxB2 increased when arachidonic acid was infused into lungs from control or treated rats. These data indicate that MCTP treatment increases the release of TxB2 from isolated lungs at a time when pulmonary hypertension is well-established, but not during early development of pulmonary hypertension.     

Cigarette smoking increases gastric luminal prostaglandin F2 alpha and thromboxane B2 in healthy smokers

Pentagastrin-stimulated gastric luminal prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, PGF2 alpha and thromboxane B2 (TxB2) were measured using a second antibody solid-phase enzyme immunoassay before, during and after cigarette smoking in healthy smokers. Smoking significantly increased PGF2 alpha and TxB2 concentration and output; in contrast no significant changes were found for PGE2 and 6-keto-PGF1 alpha levels. In addition, cigarette smoking caused a significant reduction in gastric juice volume and acid output but did not alter intragastric acidity. These findings may suggest a possible role of prostanoids in the response of the stomach to cigarette smoking.     

Changes in plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha in bronchial asthma

We measured the plasma levels of TXB2, a stable metabolite of TXA2, and 6-K-PGF1 alpha, a stable metabolite of PGI2, in 28 asthmatics (16 of extrinsic type, 12 of intrinsic type) during symptomatic period and asymptomatic period respectively with radioimmunoassay. At the same time, plasma TXB2 and 6-K-PGF1 alpha were measured in 30 normal subjects for control. The results were as follows: (1) In the extrinsic asthmatics: The plasma TXB2 level measured during symptomatic period was significantly higher than that during asymptomatic period (P less than 0.05), while the plasma level of 6-K-PGF1 alpha measured during symptomatic period was significantly lower than that of normal subjects (P less than 0.01). The ratio of TXB2/6-K-PGF1 alpha measured during symptomatic period was significantly higher than that measured during asymptomatic period and that measured in the normal subjects (P less than 0.05). (2) In intrinsic asthmatics: The plasma 6-K-PGF1 alpha level measured during symptomatic period was significantly lower than that of normal subjects. There was no significantly difference between either plasma TXB2 level or ratio of TXB2/6-K-PGF1 alpha measured during symptomatic period and that measured during asymptomatic period as well as that of normal subjects. From these results it is suggested that (1) The TXA2 and PGI2 may play a different role in different types of asthma, (2) The imbalance between TXA2-PGI2 may be one of the important factors that take part in the pathogenesis of extrinsic asthma.     

Evaluation of plasma 6-keto-prostaglandin F1 alpha and thromboxane B2 in diabetic neuropathy

The relationship between diabetic neuropathy on the one hand and microangiopathy and arteriosclerosis on the other was studied by determining plasma 6-keto-prostaglandin F1 alpha (PGF1 alpha) and plasma thromboxane B2 (TXB2) in diabetics with neuropathy. The subjects were 13 patients with insulin independent diabetes mellitus with polyneuropathy (DN+ group), 9 cases which had no neuropathy (DN- group) and 6 control cases. The patients with severe retinopathy, nephropathy and hypertension were excluded. Plasma 6-keto-PGF1 alpha and plasma TXB2 concentration were determined by radioimmunoassay. The motor neuron conduction velocity (M.C.V.) was measured through the tibial nerve in all diabetics. Plasma 6-keto-PGF1 alpha was 116.3 +/- 4.2 pg/ml (mean +/- SE) in the DN+ group and 139.9 +/- 3.0 in the DN- group, each group showing a significant fall over the control with 150.8 +/- 4.5. Plasma 6-keto-PGF1 alpha in the DN+ group showed a significant decrease in comparison with that in the DN- group. As to plasma TXB2, there was no significant difference among the three groups. The M.C.V. fell off significantly in the DN+ group with 52.9 +/- 3.2 m/sec. Furthermore, a significant positive correlation was observed between M.C.V. and plasma 6-keto-PGF1 alpha. The following is the summary of these results. A decrease in plasma 6-keto-PGF1 alpha was observed in diabetics with polyneuropathy. A decrease in the production of prostacyclin (PGI2) due to impairment of vascular endothelium in the nerve tissue was surmised. The decrease in plasma 6-keto-PGF1 alpha presumably stimulates the activity of platelet agglutination and causes an ischemic change in the nerve tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies on the interrelation of plasma 6-keto-prostaglandin F1 alpha, thromboxane B2 and diabetic microangiopathy

Plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2 (TXB2) were measured in 55 diabetics and 30 controls with radioimmunoassay. The correlation between diabetic microangiopathy and the ratio of TXB2 and 6-keto-PGF1 alpha was analysed. Diabetics were divided into three groups according to the change of retina and renal function. Group A, diabetics without microangiopathy; group B, diabetics with slight microangiopathy; and group C, diabetics with severe microangiopathy. The results showed that the ratio of TXB2/6-keto-PGF1 alpha was higher in B and C groups (0.997 +/- 0.31 1.10 +/- 0.25 means +/- S) than in the controls (0.72 +/- 0.17 means +/- S) (P less than 0.01). Group A patients had slightly higher level of the ratio (0.85 +/- 0.20 means +/- S) than the controls but the difference was not significant. The results suggest that the TXB2 and 6-keto-PGF1 alpha imbalance exists only in diabetics with microangiopathy and their imbalance might have more significance in the pathogenesis of diabetic microangiopathy than their individual change.     

Lack of specific binding of prostaglandin E2, prostaglandin F2 alpha, and 6-keto prostaglandin F1 alpha to serum in patients with peptic ulcer disease and in healthy subjects

Rabbits immunized against prostaglandins develop antibodies to prostaglandins and peptic ulcer disease (duodenal and gastric ulcers). We have evaluated the hypothesis that idiopathic gastric or duodenal ulcer disease in humans may be associated with the spontaneous occurrence of serum antibodies directed against endogenous prostaglandins. We found that serum from 45 ulcer patients (34 duodenal, 11 gastric) had a low degree of binding of radiolabeled prostaglandin E2, prostaglandin F2 alpha, or 6-keto prostaglandin F1 alpha. The extent to which prostaglandins were bound to serum of ulcer patients was not statistically different from prostaglandin binding to serum from 25 normal subjects. Therefore, we conclude that spontaneous occurrence of circulating antibodies against endogenous prostaglandins is an unlikely cause of gastroduodenal ulceration in humans.     

A study of the role of plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha in epidemic hemorrhagic fever

Plasma concentrations of Thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were dynamically measured with radioimmunoassay in 30 patients of epidemic hemorrhagic fever (EHF). It was found that the levels plasma TXB2 significantly increased and 6-keto-PGF1 alpha decreased in EHF patients as compared with those in controls. The more severe the patient's condition, the higher the level of TXB2 and the lower the level of 6-keto-PGF1 alpha. The ratio of TXB2/6-keto-PGF1 alpha was parallel with the severity of the patient's condition. Plasma TXB and TXB2/6-keto-PGF1 alpha ratio increased significantly in the hemorrhagic and shock group, while 6-keto-PGF1 alpha decreased significantly in the shock group. The results showed that there is a distinct imbalance of TXA2-PGI2 mediated through the increase of TXA2 and decrease of PGI2 in EHF. The imbalance of TXA2-PGI2 participates in the pathogenesis and pathophysiology of hemorrhage, shock and renal dysfunction.     

Urinary excretion of 6-keto-prostaglandin F1 alpha, thromboxane B2 and prostaglandin E2 in cirrhosis with ascites. Relationship to functional renal failure (hepatorenal syndrome)

The aim of the study was to investigate the urinary excretion of 6-keto-PGF1 alpha (a stable metabolite of PGI2), thromboxane B2 (TxB2; a stable metabolite of TxA2), and PGE2 in 18 normal subjects, 49 cirrhotics with ascites without renal failure (GFR = 90 +/- 4 ml/min, means +/- S.E.M.) and 20 cirrhotics with functional renal failure (FRF) (GFR = 36 +/- 3). The study was made after 5 days on a 50 mEq sodium diet and without diuretics. Plasma renin activity (PRA), plasma norepinephrine concentration (NE) and plasma antidiuretic hormone concentration (ADH) were also measured. Cirrhotics without FRF showed a significantly higher urinary excretion of 6-keto-PGF1 alpha, TxB2 and PGE, (15.9 +/- 1.7 ng/h, 3.0 +/- 0.3 ng/h, and 6.2 +/- 1.0 ng/h) than did normal subjects (9.2 +/- 0.9, 1.3 +/- 0.1 and 2.3 +/- 0.4). On the contrary, the urinary excretion of these prostaglandins was normal or reduced in patients with FRF (5.3 +/- 0.8, 1.3 +/- 0.2 and 1.9 +/- 0.4). PRA, NE and ADH were significantly increased in cirrhotics with FRF (15.2 +/- 3.9 ng/ml/h, 1026 +/- 149 pg/ml and 4.1 +/- 0.3 pg/ml) and in patients without FRF (8.0 +/- 1.4, 667 +/- 67 and 3.9 +/- 0.3) as compared to normal controls (1.3 +/- 0.2, 275 +/- 46 and 2.4 +/- 0.2). These results suggest that renal hemodynamics in cirrhosis depends upon a critical equilibrium between the activity of endogenous vasoconstrictor systems and the renal production of the vasodilator prostaglandins PGI2 and PGE2. In addition, they do not support FRF in cirrhosis being related to an increased renal production of the vasoconstrictor prostaglandin TxA2.     

Oxidation of plasma alpha 1-antitrypsin in smokers and nonsmokers and by an oxidizing agent

The inhibitor activity of the protease inhibitor alpha 1-antitrypsin (alpha 1-protease inhibitor) is decreased by oxidizing agents such as those found in cigarette smoke. We have compared specific elastase and specific trypsin inhibitor activity, under defined conditions, in 26 smokers and 26 nonsmokers. Contrary to some previous reports, we have not found a difference between them. The oxidizing agent chloramine T was used to provide an additional oxidant stress for the comparison of plasma from nonsmokers and smokers. Although there was considerable variation between individual subjects in the extent of inactivation of inhibitor activity of alpha 1-antitrypsin, there was no significant difference between nonsmokers and smokers. Apparently there was sufficient antioxidant activity in the plasma of the smokers we tested to prevent the detection of oxidized inactivated alpha 1-antitrypsin.     

盐敏感性高血压病患者血浆血栓素B2、6-酮-前列腺素F1α水平的变化及意义

目的探讨盐敏感性高血压病患者血浆血栓素B2(TXB2)、6-酮-前列腺素F1α(6-k-PG-F1α)水平的变化及意义.方法采用改良的Sullivan急性口服盐水负荷试验的方法将60例高血压病患者分为盐敏感性(SS,28例)和非盐敏感性(NSS,32例)两组.30例正常人为对照组.采用放射免疫法测定其血浆TXB2和6-k-PGF1α水平.结果SS高血压病组血浆TXB2水平[(48.76±21.34)pg/ml]显著高于NSS高血压病组[(31.67±5.30)pg/ml]及正常组[(30.01±7.72)pg/ml](P均＜0.01);SS高血压病组血浆6-k-PGF1α水平[(62.67±17.14)pg/ml]明显低于NSS高血压病组[(92.70±33.72)pg/ml]及正常组[(93.40±20.40)pg/ml](P均＜0.01);NSS高血压病组与正常组间血浆TXB2和6-k-PGF1α水平均无显著性差异(P均＞0.05).结论SS高血压病患者存在血管内皮功能受损和血小板活性增强.     

Effects of nicotine and cigarette smoke extracts on plasma level of complement C3a and C5a, thromboxane B2 and 6-keto PGF1 alpha in rabbits

In the present investigation we measured plasma levels of complement C3a and C5a, thromboxane B2 (TxB2) and 6-keto PGF1 alpha in anesthetized rabbits by radioimmunoassay after the intravenous injection of nicotine and cigarette smoke extracts. Plasma levels of complement C3a in rabbits showed a significant increased and reached a maximum value 60 minutes after the intravenous injection of nicotine and cigarette smoke extract. Plasma levels of complement C5a in rabbits showed a significant increase and reached a maximum value 30 minutes after the intravenous injection of nicotine. Plasma levels of complement C5a in rabbits showed a significant increase and reached a maximum value 60 minutes after the intravenous injection of cigarette smoke extract. Plasma levels of TxB2 in rabbits showed a significant increase after the intravenous injection of nicotine and cigarette smoke extract. Plasma levels of 6-keto PGF1 alpha in rabbits did not show any change after the intravenous injection of nicotine and cigarette smoke extracts. The above results may suggest that the intravenous injection of nicotine and cigarette smoke extracts induces an increase of plasma levels of complement C3a and C5a and TxB2 in anesthetized rabbits.     

Prostaglandin E, thromboxane B2 and 6-oxo-prostaglandin F1 alpha in amniotic fluid and maternal plasma of rhesus monkeys (Macaca mulatta) during the latter third of gestation.

The concentrations of prostaglandin E (PGE), thromboxane B2 (TXB2) and 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) were measured by radioimmunoassay in serial samples of amniotic fluid and maternal peripheral plasma in the latter third of pregnancy in rhesus monkeys (Macaca mulatta). The samples were collected under ketamine-induced anaesthesia. The concentration of PGE was undetectable in amniotic fluid until a few days before delivery when a large increase was observed in three of the five animals. There were small increases of TXB2 and 6-oxo-PGF1 alpha in amniotic fluid before delivery. In maternal plasma the concentrations of PGE, TXB2 and 6-oxo-PGF1 alpha were generally higher and more variable than in amniotic fluid and did not increase with advancing gestation. It is suggested that increased production of primary prostaglandins occurs before, and is involved in, the onset of parturition in the rhesus monkey.     

Raised levels of F(2)-isoprostanes and prostaglandin F(2alpha) in different rheumatic diseases

OBJECTIVE: To evaluate oxidative injury and inflammatory status in various rheumatic diseases by measuring the levels of isoprostanes and prostaglandins in serum and synovial fluid. METHODS: The concentrations of 8-iso-PGF(2alpha) (F(2)-isoprostane indicating oxidative injury) and 15-keto-dihydro-PGF(2alpha) (a major metabolite of prostaglandin F(2alpha)) were measured in both serum and synovial fluid aspirated from 26 patients with various arthritic diseases, including rheumatoid arthritis (RA), reactive arthritis (ReA), psoriatic arthritis (PsA), and osteoarthritis (OA). These prostaglandin derivatives were also measured in serum samples collected from 42 healthy control subjects. RESULTS: Overall, serum levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) were much higher in patients with arthritic diseases than in the healthy control subjects. The levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) in synovial fluid aspirated from knee joints were also high and varied among various types of arthritic patients. Although the synovial fluid level of these prostaglandin derivatives was sometimes higher than in the corresponding serum sample, this was not a consistent finding. Overall, there was no correlation between serum and synovial fluid levels of 8-iso-PGF(2alpha), or between serum and synovial fluid levels of 15-keto-dihydro-PGF(2alpha). However, a strong relation was found between the levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha,) in both serum (r(s)=0.53, p<0.001) and synovial fluid (r(s)=0.62, p<0.001). CONCLUSIONS: These data suggest that both free radical mediated oxidative injury and cyclo-oxygenase dependent inflammatory responses are closely correlated in various types of arthritis.     

Plasma thromboxane B2, 6-keto PGF1 alpha and cyclic nucleotides levels as related to treadmill exercise test in patients with ischemic heart disease

Plasma prostanoids and levels of cyclic nucleotides were studied in forty-nine outpatients with precordial pains and subjected to the treadmill exercise test. Blood samples were drawn before, immediately after and 30 minutes after exercise, from antecubital veins. Plasma TXB2, 6-keto PGF1 alpha, cyclic AMP and cyclic GMP levels were measured by radioimmunoassay. The results of exercise tests were evaluated according to the treadmill exercise score (TES) of Hollenberg et al. Patients were divided into two groups; those with TES (-) with ischemic findings in exercise and those with TES (+) with normal exercise response. There were no differences in TXB2 levels between the two groups before exercise. Immediately after exercise statistically significant differences in TXB2 levels were present between the two groups. There were increased levels in the TES (-) group and decreased levels in the TES (+) group (p less than 0.01). Although the 6-keto PGF1 alpha levels were the same between the two groups before exercise, 6-keto PGF1 alpha levels in the TES (+) group increased significantly immediately after exercise. Similar changes were noted in the case of cyclic nucleotides, and the differences increased immediately after exercise. We conclude that high responses of cyclic nucleotides and PGI2 are required to counteract increases in levels of TXA2 and diminution of these responses may be an important phenomenon involved in the physiological status of ischemic heart disease.