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This study aimed to investigate the metabolite differences between patients with keratoconus and control subjects and identify potential serum biomarkers for keratoconus using a non-targeted metabolomics approach. Venous blood samples were obtained from patients with keratoconus (n = 20) as well as from age-, gender- and race-matched control subjects (n = 20). Metabolites extracted from serum were separated and analyzed by liquid chromatography/quadrupole time-of-flight mass spectrometer. Processing of raw data and analysis of the data files was performed using Agilent Mass Hunter Qualitative software. The identified metabolites were subjected to a principal component and hierarchical cluster analysis. Appropriate statistical tests were used to analyze the metabolomic profiling data. Together, the analysis revealed that the dehydroepiandrosterone sulfate from the steroidal hormone synthesis pathway was significantly upregulated in patients with keratoconus (p < 0.05). Also, a combination of eicosanoids from the arachidonic acid pathway, mainly prostaglandin F2α, prostaglandin A2, 16,16-dimethyl prostaglandin E2, and 5-hydroxyeicosatetraenoic acid were collectively up-regulated as a group in keratoconus patients (p < 0.05). On the other hand, glycerophospholipid PS(17:2(9Z,12Z)/20:4(5Z,8Z,11Z,14Z)) was found to be significantly upregulated in the metabolomics profiles of control subjects (p < 0.05). The differently regulated metabolites provide insights into the pathophysiology of keratoconus and could potentially be used as biomarkers for keratoconus to aid in screening for individuals at risk hence, enabling early diagnosis and timely monitoring of disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). Although alveolar hypoxia is considered as a main cause of PH in COPD, structural and functional changes of pulmonary circulation are apparent at the initial stage of COPD. We hypothesized that an inflammatory response and oxidative stress might contribute to the formation of PH in COPD., Methods: We measured the levels of interleukin-6 (IL-6) and 8-iso-prostaglandin (8-iso-PSG) in exhaled breath condensate (EBC) and serum in 40 patients with COPD only or in 45 patients with COPD combined with PH. Pulmonary arterial systolic pressure (PASP) was assessed by Doppler echocardiography and defined as PH when the value of systolic pressure was greater than 40 mmHg., Results: Compared with the COPD only group, the level of IL-6 in EBC was significantly increased in all 45 patients with COPD combined with PH ((8.27±2.14) ng/L vs. (4.95±1.19) ng/L, P < 0.01). The level of IL-6 in serum was also elevated in patients with COPD combined with PH compared with the COPD only group ((72.8±21.6) ng/L vs. (43.58±13.38) ng/L, P < 0.01). Similarly, we also observed a significant increase in the level of 8-iso-PSG in both EBC and serum in the COPD with PH group, compared with the COPD only group (EBC: (9.00±2.49) ng/L vs. (5.96±2.31) ng/L, P < 0.01 and serum: (41.87±9.75) ng/L vs. (27.79±11.09) ng/L, P < 0.01). Additionally, the value of PASP in the PH group was confirmed to be positively correlated with the increase in the levels of IL-6 and 8-iso-PSG in both EBC and serum (r = 0.477-0.589, P < 0.05)., Conclusion: The increase in the levels of IL-6 and 8-iso-PSG in EBC and serum correlates with the pathogenesis of PH in COPD.

Evidence suggests that higher plasma carotenoid concentrations are protective in relation to breast cancer recurrence. This simple randomized carrot juice intervention study was designed to test the hypothesis that daily intake of 8 ounces of fresh BetaSweet (anthocyanin-rich) or Balero orange carrot juice would increase plasma total carotenoid concentrations to levels previously shown to be associated with reduced breast cancer recurrence. It was hypothesized that regular carrot juice intake would be associated with reductions in oxidative stress (8-iso-PGF2α) and inflammation (thromboxane B2, prostaglandin E2 metabolites, and hsC-reactive protein). Sixty-nine overweight breast cancer survivors consumed fresh carrot juice made from study-provided carrots for 3 wk. Total plasma carotenoids increased by 1.65 and 1.38 umol/L for the BetaSweet and Balero carrot juice, respectively. Rise in total plasma carotenoids for the overall sample was inversely associated with 8-iso-PGFα (OR: 0.13; 95% CI: 0.20 to 0.75; no differences were shown by carrot variety. These results suggest daily intake of fresh carrot juice is a simple and effective approach to increasing plasma total carotenoids and in turn reducing oxidative stress, but not inflammatory markers, in women previously treated for breast cancer.

Lung capacity to regulate the level of plasma prostanoids at the expense of their destruction or extra synthesis is one of their numerous non-gas-exchange functions. Prostaglandins A, E, and F, prostacyclin, and thromboxane were measured in the arterial and venous blood of 23 patients before and after surgery. The level of prostanoids was sharply increased in surgical patients. Substrates with the broncho- and vasoconstrictive action predominate in the blood of patients with obstructive and restrictive changes in the lungs, this eventually leading to complications in the postoperative period.

The prevalence of high total IgE serum levels was evaluated in 232 consecutive patients suffering from peptic ulcer. Twenty-one percent of the patients presented total IgE serum levels above 200 KU/L compared with the 5% found in a healthy control population (p < 0.004). Similar prevalence was found in gastric and/or duodenal ulcers. No significant differences in the duration of the disease, smoking habits, familiarity for peptic ulcer, symptomatology and frequency of complications were observed between patients with high and with normal total IgE serum levels. Gastric function studies (gastric acid secretion, serum pepsinogen and gastrin levels) did not show any significant differences between the two groups. The incidence of Helicobacter pylori infection was 65% in patients with normal IgE levels and 75% in those with high IgE levels (p: n.s.). The response to treatment with full dose of H2-receptor antagonists was comparable in both groups (91.25% and 90.7% of ulcer healing after 6-8 weeks of treatment). A relapse of the ulcer after 6 months of maintenance therapy (half dose of H2-receptor antagonists) was observed in 39.5% of the patients with ulcer and high total IgE serum as against the 11.9% observed in patients with normal IgE (p < 0.001). These data lend further support to the hypothesis of an underlying immuno-allergic reaction in some forms of gastric or duodenal ulcer.

The plasma levels of prostaglandins A, E, and F2 alpha were measured by the radioimmunoassay in 146 hypertensive and 62 healthy pregnant females. It was ascertained that beginning in the second trimester, the ratio of various prostaglandins is impaired in the direction of increasing values of substances from the pressor group as the hypertensive disease evolves. This is due to lower levels of prostaglandins A and E and/or higher levels of prostaglandins F2 alpha. In associated late gestosis, prostaglandin levels are related to the clinical manifestations of this disease. There are increased prostaglandin F2 alpha concentrations with severe nephropathy. The studies indicate that prostaglandins affect the course of hypertensive disease in pregnant women and the development of associated late gestosis.

Prostaglandin (PG) A and E content in the blood and renal tissues (cortex and medulla) has been studied in 25 dogs in the early phase of acute renal failure (ARF). It has been found that by the 4th hour of compression PG content increases drastically in the blood and renal cortex and decreases in the renal medulla. Compression relief and ARF progress were accompanied by a drop in PG concentration both in the blood and the renal cortex and medulla. It is concluded that enhanced PGE2 synthesis is a protective reaction preventing the damage of the renal structure and function. The following decrease in PGE2 level is mediated by progressing effect of aggressive factors on the interstitial cells of the renal medulla and the endothelial cells of the cortex vessels--as a basic source of endogenous PG synthesis. The results obtained are experimental proof of PGE2 use in the complex therapy of ARF.

Three patients with the hepatorenal syndrome were treated with prostaglandin E1 administered through a selective renal arterial catheter. Prostaglandin E1 was given in progressively increasing doses (2 to 100 ng/kg/min) over a 60-minute period. Control plasma prostaglandin E levels were elevated in all three patients, 0.98, 0.91, and 0.83 ng/ml, respectively. At the end of the infusion, plasma prostaglandin E levels had risen to 10.4, 2.63, and 10.3 ng/ml in the three patients respectively. Plasma renin activity increased during the course of the infusion in two of the patients. The plasma aldosterone concentration did not change during the prostaglandin E1 infusion. Intrarenal prostaglandin E1 failed to increase urine volume or urinary sodium concentration in three patients with the hepatorenal syndrome.

Venous prostaglandins A, E, and F were determined by radioimmunoassay in 10 dogs before and one hour after administration of sodium pentobarbital (35 mg/Kg, iv). In the conscious state, PGA was 0.34 + 0.04 ng/ml (mean +/- SE), PGE 0.20 + 0.01 ng/ml, and PGF 0.25 + 0.03 ng/ml. During pentobarbital anesthesia, these levels were unchanged (p greater than 0.05). Thus, pentobarbital anesthesia had no effect on peripheral venous prostaglandin levels.

The role of the renin-angiotensin system and prostaglandins in the regulation of fetal vascular homeostasis was investigated by measuring hemodynamic and hormonal responses to fetal administration of frusemide in ten intact and five bilaterally nephrectomised fetal lambs. The increase in fetal arterial pH and the fall in pCO2 following treatment with frusemide suggests that this drug may influence placental exchange of blood gases. The increase in plasma renin activity without accompanying changes in plasma PGE does not support a direct relationship between renin release and renal prostaglandin E production in the fetal lamb.

An estimation of renal secretion rates of PGE2 and PGF2 alpha, in parallel with renin-angiotensin-aldosterone system and catecholamines was performed on control subjects, essential hypertensive, and renovascular hypertensive patients. In essential hypertensive patients with normal plasma renin activity (PRA) and normal catecholamines level. We did not find any changes in the renal prostaglandin (PG) secretion rate as compared to the control subjects. Our results do not support the hypothesis that a reduction of PGE2 production is a specific feature of patients with essential hypertension. In renovascular hypertensive patients with unilateral renal artery stenosis we found: 1. High PRA in the renal plasma of the abnormal (with renal artery stenosis) kidney, and in peripheral plasma; 2. Decreased renal release of PGE2 from both kidneys, more distinct in abnormal kidney; 3. No changes of renal production of PGF2 alpha. The positive and negative correlation between renin-angiotensin system and renal PGs in physiological and pathological conditions was discussed.

Aspirin, salicylic acid and indomethacin reversibly inhibit prostaglandin binding to human serum proteins. This effect was demonstrated in the sera of normal subjects and of rheumatoid arthritis patients treated with aspirin as well as by addition of these drugs to serum in vitro. The displacement of serum prostaglandins by salicylate is likely to affect the kinetics of prostaglandin transport and may facilitate the delivery of prostaglandins from serum to tissue receptors.

Plasma levels of PGE2, PGA2 and PGF2 alpha were determined by radioimmunoassay in maternal cubital vein blood of 210 women and once during pregnancy. In the course of pregnancy plasma levels of these prostaglandins varied considerably: 0,09-1,83 ng PGE2/ml, 0,12-2,8 ng PGA2/ml and 0,04-0,5 ng PGF2 alpha/ml. At term (40 and 41th week) prostaglandin levels were found to be low and within a range of: 0,15-0,25 ng PGE2/ml; 0,12-0,23 ng PGA2/ml and 0,2-0,3 ng PGF2 alpha/ml. Determination of prostaglandin levels in numerous samples from different women during pregnancy did not show continuous changes nor in the pattern of the distribution of PGE2, PGA2 and PGF2 alpha.

During both phases of their menstrual cycle, women who suffer from benign mastopathies evidence hormonal deficiency, which is total although of variable magnitude, as shown by oestradiol (E2) and progesterone (p) plasma levels. by contrast, these women show a concomitant and large rise of prostaglandin E2 (PGE2) plasma level. An oestrogen directed PGE2 synthesis by the mammary epithelium is likely to occur. The patients whose mammary thermography displays PG synthesis can be cooled by the administration of PG synthesis inhibitors. They show a steroid deficiency which is more or less pronounced without having any marked imbalance of the E2-P ratio. By contrast, patients who exhibit no thermographic response show a marked relative rise in oestrogen during both phases of the menstrual cycle. The significance of PG synthesis and relatively raised oestrogen levels will be discussed in relationship to the risk of breast cancer.

The role of prostaglandin A (PG A) in the pathogenesis of renal hypertension has been studied. The concentration of endogenous PG A was measured in the peripheral plasma by radioimmunoassay in patients with chronic renal disease and in control subjects. The mean plasma concentration of PG A1 equivalents was as follows: 1. normotensive healthy volunteers (n=23): 115 +/- 15 pg/ml 2. patients in terminal renal failure on regular hemodialysis a) anephric patients (n=6): 51+/- 21 pg/ml b) patients retaining their own kidneys, all but one with hypertension (n=9): 231 +/- 51 pg/ml (P less than 0.01 versus control) 3. patients with chronic renal disease a) with hypertension (n=7): 204 +/- 60 pg/ml (P less than 0.01 versus control) b) without hypertension (n=11): 136 +/- 30 pg/ml. Renal hypertension was associated with high levels of PG A in peripheral blood. This increase is probably a secondary adaptative mechanism for the excretion of a greater fraction of the glomerular filtrate at a lower blood pressure. PG A may represent a circulating "antihypertensive hormones".

The present study evaluates the response of the nonpregnant ewe, the pregnant ewe, and the fetal lamb with regard to prostaglandin physiology after E. coli endotoxin administration. Baseline levels are reported and response to a stimulator (E. coli endotoxin) and an inhibitor (indomethacin) of prostaglandin synthesis is evaluated. The results reveal that the prostaglandin response to stimulation or inhibition relies upon the baseline levels and that acute alterations of prostaglandin ratios may occur with inhibition of prostaglandin synthesis. The fetus reacts differently than the pregnant and nonpregnant animal and appears to be resistant to the effects of endotoxin, which may be secondary to the elevated baseline fetal prostaglandin levels.

When prostaglandin A1 was incubated with a Tris/saline suspension of washed human red blood cells, a substantial amount was converted to polar metabolites. These were purified by solvent extraction, XAD-2 column, and cellulose thin layer chromatography and characterized by chromatography, amino acid analysis, and mass spectrometry. The polar metabolites were a mixture of two glutathione conjugates of prostaglandin A1. The first (approximately 40%) was identical with the product of the nonenzymic reaction of glutathione with prostaglandin A1. The second (approximately 60%) was formed from the first by reduction of the 9-keto group of the prostaglandin moiety. The latter compound was also prepared synthetically by treating the glutathione conjugate of prostaglandin A1 with sodium borohydride.

Plasma levels of PGE2, PGA2 and PGF2 alpha were determined by radioimmunoassay in maternal venous blood during different phases of uterine contractions. Mean prostaglandin levels during labor were: PGE2 = 2,25 +/- 1,3 ng/ml (mean +/- SD), PGA2 = 2,86 +/- 1,55 ng/ml and PGF2 alpha = 0,58 +/- 0,37 ng/ml. The approximate ratios between the prostaglandin concentrations were: PGE2:PGA2: PGF2 alpha = 1:1-3:0,3. No changes of PGE2 levels were found in the course of concentrations during the first and second stage of labor. At delivery and at the contraction followed by the expulsion of the placenta, PGE2 concentrations rose from the beginning of the contraction (2,21 +/- 0,07 ng PGE2/ml) to the maximum of the contraction (4,31 +/- 0,56 ng PGE2/ml). PGA2 levels did neither show a correlation to the course of contractions nor to the different stages of labor, but were considerably different between patients during the first stage of labor (e.g. 1,9 +/- 1,1 ng PGA2/ml) and during the second stage of labor (3,36 +/- 2,8 ng PGA2/ml). Mean PGF2 alpha concentrations were between 0,21 +/- 0,12 ngPGF2 alpha/ml (1st stage) and 0,81 +/- 0,11 ng PGF2alpha/ml (highest value obtained, 1st stage of labor, too). There was no correlation between PGF2 alpha concentrations and the course of contractions during the different stages of labor.

Increased renal prostaglandins activated by beta-catecholamines could produce renal tubular sodium wasting and angiotensin pressor resistance observed in Bartter's syndrome. We therefore measured plasma renin activity (PRA), aldosterone and prostaglandin A (PGA) by radioimmunoassay, and body composition by isotope dilution prior to and following beta-adrenergic blockade with propranolol (200 mg/day for 4 days) and prostaglandin synthesis inhibition by indomethacin (200 mg/day for 4 days) in a patient with Bartter's syndrome on a 250 meq sodium diet. After the administration of propranolol, body weight increased 3 kg, daily urine sodium decreased within 24 hours from 230 to 64 meq, and urine potassium from 102 to 45 meq, but PRA and the aldosterone level remained elevated. With the administration of indomethacin, body weight increased 5 kg, daily urinary sodium decreased within 24 hours to 11meq and urine potassium to 16 meq, PRA (normal less than 3 ng/100 ml/hour) decreased from 55 to 4.3 ng/ml/hour, plasma aldosterone (normal less than 8 ng/100 ml) from 74.1 to 3.6 ng/100 ml, and whole blood PGA (normal 546 +/- 307 pg/ml) decreased from 1,390 and 945 to 86 pg/ml. After the administration of propranolol or indomethacin, exchangeable sodium, total body water, extracellular volume and plasma volume all increased from less than to greater than predicted, and pressor resistance to angiotensin was normalized. These results suggest that Bartter's syndrome results from beta adrenergic and prostaglandin-mediated proximal tubular rejection of sodium leading to increased distal sodium-potassium exchange.

From the blood plasma of 34 patients with ischemic heart disease and hyperlipoproteinemia and without it and in 10 practically healthy persons prostaglandins E, A and F2alpha were isolated and the proportion of each one of them was determined by the radioimmunological method. Changes in the quantitative composition of the blood plasma prostaglandins in patients with ischemic heart disease and hyperlipoproteinemia were disclosed, these changes suggesting the participation of the substances in question in the pathogenesis of atherosclerosis.

The relation between renal vein renin activity (RVRA) and renal vein-prostaglandin A (PGA) and prostaglandin E (PGE) concentrations was examined in 50 patients with hypertension who underwent renal vein catheterizations for suspected renovascular hypertension. In 14 patients wih unilateral renal artery stenosis, mean renal vein PGE concentrations were higher in the renal vein draining the nonischemic kidney, while RVRA was increased in the renal vein draining the ischemic kidney. PGE ratios from the two sides were inversely related to RVRA ratios in this group. In the other 36 patients with either bilateral renal artery stenosis, essential hypertension or nonrenovascular unilateral renal disease, RVRA and PGE concentrations were similar in both kidneys. No relation between RVRA and PGA could be established for any group.

Prostaglandins (PGA1, PGE1 and PGF2 alpha) were assayed in 15 patients with chronic coronary disease during an anginal attack induced through frequent atrial stimulation. Measurements from eleven patients with intact coronary arteries served as control. Lactate extraction coefficient was used as a biochemical indicator of myocardial ischemia; the latter was associated with increased production of coronary sinus PGF2 alpha and arterial PGA1. No correlation could be established between PG levels in the studied series, the extent of ST depression on electrocardiograms, lactate extraction level and hemodynamic manifestations.

A specific, sensitive and accurate radioimmunoassay (RIA) method for the measurement of prostaglandin A1 (PGA1) in either human whole blood or plasma is described. Whole blood is immediately lysed with distilled water containing tritiated indicator. When plasma is assayed, the blood samples are handled at 4 C and rapidly centrifuged. The lysate or plasma is adjusted to pH 5 with buffer and quickly extracted with 5% methanol in dichloromethane. The whole blood or plasma extract is then purified by Sephadex LH20 chromatography using the system methanol: methylene chloride (5:95) which separates the major groups of PGA, PGE and PGF. The RIA is then performed using an antiserum generated in rabbits from PGA1 coupled to bovine thyroglobulin. The antibody is highly specific, possessing very low cross reactivity to other prostaglandins (PGA2, PGE, PGB and PGF). Activated florisil or ammonium sulfate can be used to separate bound from free prostaglandin. This whole blood or plasma method yields blank values of only 2 +/- 2 pg per sample with a between assay precision determined by duplicate analysis of 8% and interassay precision of 3%. The mean whole blood PGA1 concentration in 27 subjects in 2.5 +/- 1.6 (SD) ng per 100 ml. No significant sex difference in PGA1 levels was noted and values were similar whether measured in whole blood or cooled plasma rapidly prepared and extracted. These values of PGA1 are much lower than those RIA values reported by others for "PGA" using antibodies with lower specificities.

The behaviour of prostaglandins A, B, E 1, E 2, F 1 and F 2 has been examined in the granulocytes and lymphocytes of the peripheral blood of normal subjects and in circulating leucocytes of patients with CML, AML, CLL and ALL. At the same time, modifications of PGE 2 in the granulocytes of normal subjects and in patients with CML or AML before and after phagocytosis of latex particles were monitored. The general observation was a lowering in PGE and PGF in acute myeloid and lymphatic leukaemia, while the variations in CML and CLL were rather complex. Also observed was a reduction in PGE 2 in AML but not in CML, including a reduced response to phagocytosis in granulocytes. The data are compared with previous reports of AMPc and GMPc in the same cells and commented on, taking into consideration their possible reflexion on the proliferative and functional activity of the cells examined.

Plasma immunoreactive prostaglandin A (iPGA) values were determined for 14 premature infants before and after 48 hours of phototherapy and in a control group of six age-matched premature infants. At 4 to 8 days of life, the infants who had received phototherapy for 48 hours had significantly lower iPGA values compared with controls. At 2 to 3 days of life, four infants with a clinically apparent patent ductus arteriosus were found to have significantly elevated iPGA values compared with controls. After 48 hours of phototherapy, these infants likewise had a significant decrease in iPGA values compared with controls; in all four infants, the ductus closed spontaneously. Phototherapy is an effective method for decreasing plasma iPGA values in premature infants.

The plasma concentrations, tissue distribution and excretion of prostaglandin A1 (PGA1) and related metabolites have been determined in rats, following the intravenous injection of a single dose of PGA1-5,6-3H. Urinary and faecal excretion accounted for averages of 25 and 43% of the administered dose of PGA1, respectively. Oxidative cleavage of the carboxyl side chain of PGA1 appeared to be a major metabolic pathway in the rat. PGA1-5,6-3H was deemed unsuitable for metabolism studies in man, in view of the significant loss of tritium label from the prostaglandin;

Twenty-four and 48 hours after injection of chorionic gonadotropin (CG) the content of prostaglandins E + A in the liver and blood plasma of white random-bred rats with chronic hepatitis increases (both after and without castration). This accounts for some aspects of the mechanism of the CG-induced stimulation of liver regeneration, which results in structural and functional normalization of the organ.

Levels of PGE in renal venous blood were found to be significantly elevated at the time RBF was increased by furosemide. Following indomethacin, a second dose of furosemide failed to increase RBF and levels of PGE in renal venous blood were not elevated. Levels of PGF and PGA were not affected by furosemide. The increase of PGE in renal venous blood at the time of renal dilation supports the hypothesis that furosemide increases RBF by releasing PGE. An intrarenal action of the released PGE is implied by this mechanism.

The effect of angiotensin II on peripheral levels of immunoreactive prostaglandin A2 (IR-PGA) was determined in 17 normal male volunteers. IR-PGA rose from 338 +/-65 (SE) pg/ml to 635+/-142 in response to pressor infusions of angiotensin II (p less than 0.05 on paired analysis). This increase was not observed when indomethacin, 75 mg p.o., was given to 8 patients two hours prior to a repeat infusion. Five patients of the original group were placed on a low sodium diet (10-20 mEg). The response to angiotensin was now exaggerated (278+/-52 pg/ml to 916+/-284). These five patients were kept on a low sodium intake and given indomethacin 50 mg p.o. g 6 hourly for 4 days. There was no significant rise with angiotensin infusion (106+/-31 pg/ml to 120+/-70). Pressor infusions of angiotensin II raise peripheral levels of IR-PGA, and this response is exaggerated by a low sodium diet and blocked by either acute or chronic indomethacin administration. This data supports the concept that vasodilatory prostaglandins may be released by endogenous angiotensin and thus provide a dynamic antagonism to the renin angiotensin system in man.

A dialysis equilibrium method for plasma or tissue preparation for radioimmunoassay of prostaglandins is presented and compared to the silica gel column technique. The plasma or tissue is extracted, dried, redissolved in buffer and dialyzed for further purification before assay. Results comparing both methods shows that dialysis equilibrium greatly simplifies the silica gel column technique yet preserves specificity, sensitivity and reproducibility. In addition a rapid micromethod for the development of a specific antibody to prostaglandin A is detailed.

Plasma prostaglandins were determined by radioimmunoassay in 92 pregnant and 14 nonpregnant women. There was significant elevation of PGA-like material in the first trimester of pregnancy (1744 pg/ml) over that seen in nonpregnant women (576 pg/ml) with continuation of that elevation in the second and third trimesters. No significant difference existed among PGE levels of the nonpregnant group (251 pg/ml) and the first two trimesters of pregnancy (384 pg/ml and 294 pg/ml); the PGE level of the third trimester group (443 pg/ml) was significantly elevated over that of the nonpregnant group. PGF levels remained constant during all trimesters (135 pg/ml, 144 pg/ml, and 130 pg/ml) but exhibited plasma concentrations significantly higher than the nonpregnant group (78 pg/ml). Potential role (s) of prostaglandins as mediators of cardiovascular and renal changes of pregnancy are discussed.

Current concepts of atherogenesis based on animal and human investigations indicate prostaglandins as a key factor in atherosclerotic lesions. The plasma profiles of thromboxane B2 (TXB2), 6-keto-PGF1 alpha, PGE2, PGF2 alpha, and PGA1 were investigated by means of a sensitive radioimmunoassay technique in 40 patients with arteriosclerosis obliterans and in 30 healthy control subjects. Abnormally high levels of TXB2 and PGE2 (222.97 +/- 320.86 pg/ml, mean +/- SD, vs 20 +/- 2.1 and 352.66 +/- 235.54 vs 24.4 +/- 3, p less than 0.01) were detected in arteriosclerosis obliterans patients. The ratio between TXB2 and 6-keto-PGF1 alpha was increased from 1.2 in control subjects to 6.0 in patients. In arteriosclerosis obliterans TXB2 increased in relation to clinical manifestations and to the extension of the vascular damage. In addition, TXB2 was positively related to serum triglyceride content (r = 0.562, p less than 0.05) and inversely related to platelet count (r = 0.727, p less than 0.001). The marked imbalance between the stable metabolites of thromboxane and prostacyclin in arteriosclerosis obliterans patients provides biologic evidence which fits well with the thrombogenic theory of atherosclerosis. These results further support the theory that prostaglandins may be heavily involved in atherosclerosis.