15-keto-13-14-dihydroprostaglandin-f2alpha and Inflammation

Prostaglandin F2alpha (PGF2alpha), a foremost stable vasoactive cyclooxygenase (COX)-catalyzed prostaglandin, regulates a number of key physiological functions such as luteolysis, ovarian function, luteal maintenance of pregnancy, and parturition as a constitutive part of ongoing reproductive processes of the body. It has recently been implicated in the regulation of intricate pathophysiological processes, such as acute and chronic inflammation, cardiovascular and rheumatic diseases. Since the discovery of a second isoform of COXs, it has been shown that PGF2alpha can be formed in vivo from arachidonic acid through both isoforms of COXs, namely cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Being synthesized in various parts of the body, it metabolizes instantly to a number of rather inactive metabolites mainly in the lungs, liver, kidney, and efficiently excretes into the urine. 15-Keto-dihydro-PGF2alpha, a major stable metabolite of PGF2alpha that reflects in vivo PGF2alpha biosynthesis, is found in larger quantities than its parent compound in the circulation and urine in basal physiological conditions, with short-lived pulses during luteolysis, induced termination of pregnancy and parturition, and is increased in tissues and various body fluids during acute, sub-chronic, and severe chronic inflammation. Further, the close relationship of PGF2alpha with a number of risk factors for atherosclerosis indicates its major role in inflammation pathology. This review addresses multiple aspects of PGF2alpha in addition to its emerging role in physiology to inflammation.

Topics: Animals; Atherosclerosis; Body Fluids; Carbon Tetrachloride Poisoning; Carotid Arteries; Cyclooxygenase 1; Cyclooxygenase 2; Diabetes Complications; Dinoprost; Female; Humans; Inflammation; Linoleic Acids, Conjugated; Luteolysis; Myocardial Reperfusion Injury; Obesity; Pregnancy; Risk Factors; Shock, Septic; Smoking

Topics: Biomarkers; Cerebrovascular Disorders; Dinoprost; Humans; Hypercholesterolemia; Immunoenzyme Techniques; Inflammation; Kidney Diseases; Myocardial Ischemia; Oxidative Stress; Radioimmunoassay; Reference Values; Specimen Handling

Oxidative stress and inflammation may be involved in the etiology of age-related cataract. This study is the first to investigate the association between urinary levels of 8-iso-prostaglandin F₂α (PGF₂α; as a biomarker for systemic oxidative stress in vivo) and 15-keto-dihydro-PGF₂α (as a biomarker for systemic inflammation in vivo) and risk of age-related cataract. We observed in a nested case-control study, including 258 women with incident cataract diagnosis and/or cataract extraction and 258 women without cataract, matched on age and date of urine sample collection that, women with higher levels of urinary 8-iso-PGF₂α as compared with lower levels had an increased risk of age-related cataract. There was no difference in 15-keto-dihydro-PGF₂α levels between cases and controls. Our observations lead to the hypothesis that higher systemic oxidative stress increases the risk of developing age-related cataract.

Topics: Aged; Aging; Case-Control Studies; Cataract; Dinoprost; Female; Humans; Inflammation; Oxidative Stress

Pentadecanoic acid (15:0) and heptadecanoic acid (17:0), the dairy-specific saturated fatty acids have been inversely, while inflammation and oxidative stress have been positively related to the risk of cardiovascular disease (CVD). Both fatty acid metabolism and inflammation and oxidative stress may be influenced by adiposity. In the current cross-sectional analyses among adolescents (mean age 15 years), we determined whether overweight status modified the associations between dairy fatty acids (pentadecanoic acid (15:0) and heptadecanoic acid (17:0)) represented in serum phospholipids (PL) and markers of inflammation and oxidative stress. Six biomarkers for inflammation and oxidative stress were analyzed, including circulating adiponectin, C-reactive protein (CRP), cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and urinary 15-keto-dihydro-PGF2α (15-keto) and 8-iso-PGF2α (F2-iso). Generalized linear regression analyses, adjusted for age, gender, race, tanner score, total energy intake and physical activity, revealed that PL dairy fatty acids were inversely associated with CRP, F2-iso and 15-keto in overweight, but not in normal weight adolescents (all P(interaction) < 0.05). However, higher level of PL dairy fatty acids was associated with lower IL-6 among all adolescents. Further adjustment for dietary intake of calcium, vitamin D, protein, total flavonoids, and ω-3 fatty acids did not materially change the findings. Dairy-specific saturated fats, i.e., 15:0 and 17:0 fatty acids, may contribute to the potential health benefits of dairy products, especially for overweight adolescents.

Topics: Adiposity; Adolescent; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Dairy Products; Dietary Fats; Dinoprost; Fatty Acids; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Linear Models; Male; Obesity; Oxidative Stress; Phospholipids; Risk Factors

Fruit and vegetable consumption has been associated with a reduced risk of several diseases including CVD. A part of these effects seen could be linked to anti-inflammatory and antioxidative effects, although this has not been thoroughly investigated. The present study was designed to investigate the effects of the dietary intake of beta-carotene, alpha-tocopherol and ascorbic acid on in vivo biomarkers of inflammation (PGF2alpha, high-sensitive C-reactive protein (hsCRP) and IL-6 formation) and oxidative stress (F2-isoprostane formation), the two important factors associated with accelerated atherosclerosis. The dietary intake of 704 participants in the Uppsala Longitudinal Study of Adult Men (ULSAM) at age 70 years was registered and inflammatory and oxidative stress biomarkers were quantified 7 years later. The registered dietary intakes of ascorbic acid and alpha-tocopherol were negatively associated linearly and in quartiles with both PGF2alpha, hsCRP, IL-6 and F2-isoprostanes, where ascorbic acid intake generally was more strongly associated. Dietary intake of beta-carotene was only significantly negatively associated with F2-isoprostanes. In conclusion, the present study is the first to suggest that the intake of food rich in antioxidants is associated with reduced cyclo-oxygenase- and cytokine-mediated inflammation and oxidative stress at 7 years of follow-up. These associations could be linked to the beneficial effects of fruit and vegetables observed on CVD.

Topics: Aged; alpha-Tocopherol; Ascorbic Acid; beta Carotene; Biomarkers; C-Reactive Protein; Creatinine; Diet; Dinoprost; Humans; Inflammation; Interleukin-6; Linear Models; Longitudinal Studies; Male; Oxidative Stress; Vitamins

The aim of the present observational study was to investigate the relationships between glycaemic status and levels of oxidative stress and inflammation in well-controlled type 2 diabetes subjects. Metabolic variables (weight, BMI, waist circumference (waist), blood glucose, glycated Hb (HbA(1c)), insulin, blood lipids), biomarkers of oxidative stress (8-iso-PGF(2alpha), malondialdehyde, 8-oxo-7,8-dihydro-2'-deoxyguanosine, formamido pyrimidine glycosylase-sites, frequency of micronucleated erythrocytes, nitrotyrosine) and inflammatory markers (high sensitivity C-reactive protein (hsCRP), IL-6, cyclo-oxygenase-catalyzed PGF(2alpha)-metabolite) were measured. Fifty-six patients (thirty women and twenty-six men, age 62.3 (SD 7.0) years, HbA(1c) 6.1 (SD 0.9) %, BMI 28.3 (SD 3.8) kg/m(2), waist 99.6 (SD 11.1) cm) were included in the study. HbA(1c) (r 0.29, P=0.03) and blood glucose (r 0.33, P=0.01) correlated positively with 8-iso-PGF(2alpha). Positive correlations were also observed between HbA(1c) and nitrotyrosine (r 0.42, P=0.01), waist and hsCRP (r 0.37, P=0.005), hsCRP and IL-6 (r 0.61, P<0.0001) and between PGF(2alpha)-metabolite and 8-iso-PGF(2alpha) (r 0.27, P=0.048). The present study indicates that glycaemic status is associated with oxidative stress even in subjects with well-controlled type 2 diabetes. Furthermore, inflammation was more related to abdominal obesity than to glycaemic control. A large number of biomarkers of oxidative stress and inflammation were investigated, but only a few associations were found between the markers. This could be due to the fact that none of these biomarkers biosynthesises via similar pathways or simultaneously owing to their diverse nature and origin.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Deoxyguanosine; Diabetes Mellitus, Type 2; Dinoprost; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inflammation; Insulin; Interleukin-6; Lipids; Male; Malondialdehyde; Middle Aged; Obesity; Oxidative Stress; Probability; Statistics, Nonparametric; Tyrosine; Waist Circumference

Prostaglandins are profoundly involved in endotoxaemic shock. Twenty pigs were given endotoxin at various doses (0.063-16 microg kg(-1) h(-1)). Three non-endotoxaemic pigs served as controls. Two eicosanoids were measured in plasma (8-iso-PGF(2alpha), a free radical-mediated lipid peroxidation product, and 15-keto-dihydro-PGF(2alpha) a major metabolite of COX activity) and evaluated against the pathophysiological responses that occur during endotoxaemic shock. Endotoxin mediates an increase in both 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha). An increase in the endotoxin dose induced significant log-linear responses in 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha). Oxidative injury correlated to the TNF-alpha, IL-6, reductions in cardiac performance and to oxygen delivery and utilisation. COX-mediated inflammatory responses correlated to TNF-alpha, IL-6 and to reductions in arterial oxygen tension. Thus, oxidative injury and COX-mediated inflammation play a central role in the manifestation of endotoxaemic shock. Furthermore, formation of these eicosanoids on endotoxin-mediated alterations in pulmonary hypertension, oxygen delivery and oxygen utilisation seems to be independent of the administered endotoxin dose.

Topics: Animals; Dinoprost; Heart; Inflammation; Oxidative Stress; Shock, Septic; Sus scrofa; Swine

Low concentrations of selenium (Se) predict mortality and cardiovascular diseases in some populations. The effect of Se on in vivo indicators of oxidative stress and inflammation, two important features of atherosclerosis, in human populations is largely unexplored. This study investigated the longitudinal association between serum selenium (s-Se) and a golden standard indicator of oxidative stress in vivo (8-iso-prostaglandin F2alpha, a major F2-isoprostane), an indicator of cyclooxygenase (COX)-mediated inflammation (prostaglandin F2alpha), high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and serum amyloid A protein (SAA) in a follow-up study of 27 years. The s-Se was measured in 615 Swedish men at 50 years of age in a health investigation. The status of oxidative stress and inflammation was evaluated in a re-investigation 27 years later by quantification of urinary 8-iso-PGF2alpha and 15-keto-dihydro-PGF2alpha (a major metabolite of PGF2alpha) and serum hsCRP, SAA and IL-6. Men in the highest quartile of s-Se at age 50 had decreased levels of 8-iso-PGF2alpha compared to all lower quartiles and decreased levels of PGF2alpha compared to all lower quartiles at follow-up. These associations were independent of BMI, diabetes, hyperlipidemia, hypertension, smoking, alpha-tocopherol and beta-carotene at baseline. The s-Se was not associated with hsCRP, SAA or IL-6 at follow-up. In conclusion, high concentrations of s-Se predict reduced levels of oxidative stress and subclinical COX-mediated (but not cytokine-mediated) inflammation in a male population. The associations between Se, oxidative stress and inflammation, respectively, might be related to the proposed cardiovascular protective property of Se.

Topics: Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Diet; Dinoprost; Follow-Up Studies; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Isoprostanes; Longitudinal Studies; Male; Middle Aged; Oxidative Stress; Radioimmunoassay; Selenium; Serum Amyloid A Protein; Sweden

Involvement of cyclooxygenase (COX)-mediated inflammation in type 2 diabetes has not been studied, and the association between cytokine-mediated inflammation and diabetes is not fully clarified.. 15-Keto-dihydro-prostaglandin F2alpha (a metabolite of prostaglandin F2alpha and an indicator of COX-mediated inflammation), high-sensitivity C-reactive protein (CRP), serum amyloid protein A (SAA), 8-iso-PGF2alpha (a nonenzymatic, free radical product of arachidonic acid and an indicator of oxidative stress), and alpha-tocopherol were measured in a population-based sample of 77-year-old men (n=765), in which 112 men had type 2 diabetes. The inflammatory indicators were increased in men with diabetes (urinary 15-keto-dihydro-PGF2alpha, P<0.001, CRP and SAA, P<0.05). However, when adjusted for body mass index, waist circumference, or fasting insulin, no association was found between diabetes and CRP or SAA. The oxidative stress indicator 8-iso-PGF2alpha in urine was increased (P<0.01) in men with diabetes. Patients who were newly diagnosed with diabetes (<7 years since diagnosis) had increased urinary 15-keto-dihydro-PGF2alpha and decreased alpha-tocopherol, but 8-iso-PGF2alpha was unaltered.. This is the first study to show that type 2 diabetes in elderly men is related to COX-mediated inflammation, reflected by enhanced prostaglandin formation. The high levels of cytokine-mediated acute-phase proteins observed in men with diabetes appear to be related to obesity and increased fasting insulin. The results further suggest that the appearance of chronic inflammation is an early process in the pathogenesis of diabetes, whereas oxidative injury may be a later process, possibly related to inflammation.

Topics: Aged; alpha-Tocopherol; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Cohort Studies; Comorbidity; Diabetes Mellitus, Type 2; Dinoprost; Follow-Up Studies; Humans; Inflammation; Insulin; Lipids; Male; Oxidative Stress; Prostaglandin-Endoperoxide Synthases; Serum Amyloid A Protein; Sweden

This study is designed to evaluate whether oxidative stress and inflammation are involved in severe pre-eclampsia compared to normal pregnancy and non-pregnancy. We have measured plasma and urinary levels of 8-iso-PGF2alpha, a major isoprostane as an indicator of oxidative stress; plasma and urinary 15-keto-dihydro-PGF2alpha, a major metabolite of cyclooxygenase-catalysed PGF2alpha as an indicator of inflammatory response, and plasma -alpha-and -gamma-tocopherol in 18 pre-eclamptic, 19 normal pregnancy and 20 non-pregnant women. Pregnant women had significantly higher levels of 8-iso-PGF2alpha and PGF2alpha metabolite as compared to the non-pregnancy. Levels of 8-iso-PGF2alpha in the pre-eclamptic women did not differ from the normal pregnancy but PGF2alpha metabolite levels were significantly higher in normal pregnancy. On the other hand, gamma-tocopherol levels were significantly lower in pre-eclampsia than normal pregnancy. In contrast, the concentration of alpha-tocopherol was very similar between the groups. alpha-and gamma-tocopherol levels were significantly lower in pregnancy compared to non-pregnancy. Although no direct evidence of oxidative stress and inflammatory response was observed in severe pre-eclampsia, a reduction of gamma-tocopherol suggests the possible precedence of oxidative stress in this condition. Higher levels of isoprostanes and prostaglandin metabolite in late pregnancy suggest the importance of both free radicals and cyclooxygenase-catalysed oxidation products in normal biological processes of pregnancy.

Topics: Adult; alpha-Tocopherol; Antioxidants; Biomarkers; Dinoprost; Female; gamma-Tocopherol; Humans; Inflammation; Lipid Peroxidation; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Sweden

Free radicals are believed to be involved in postsurgery-related complications. We studied whether cardiopulmonary bypass (CPB) operation has any immediate impact on the initiation of oxidative stress and inflammatory response by measuring isoprostanes and prostaglandin F2alpha during and 24 h following CPB. The levels of 8-iso-PGF2alpha (a major F2-isoprostane and biomarker of oxidative stress) and 15-keto-dihydro-PGF2alpha (a major metabolite of PGF2alpha and biomarker of inflammatory response) were measured in frequently collected plasma samples before, during, and up to 24 h postsurgery in 21 patients. 8-Iso-PGF2alpha levels significantly increased within 3 min (p <.0001) and continued until 50 min (p <.0001) during CPB. On the contrary, no significant increase of inflammatory response indicator, 15-keto-dihydro-PGF2alpha was found during and up to 24 h postoperatively. These findings establish an increased free radical-induced oxidative stress activity rather than inflammatory response after CPB.

Topics: Adult; Aged; Cardiopulmonary Bypass; Dinoprost; Female; Free Radicals; Humans; Inflammation; Ischemia; Isoprostanes; Male; Middle Aged; Models, Chemical; Oxidative Stress; Oxygen; Prostaglandins; Radioimmunoassay; Time Factors

Plasma and urinary levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) were analysed at baseline and during the ischemia-reperfusion period in experimental spinal cord ischemia. A significant and immediate increase of 8-iso-PGF(2alpha) in plasma at the start and up to 60 min, and in the urine at 90-150 min following ischemia indicate an association of oxidative injury. The inflammatory response indicator 15-keto-dihydro-PGF(2alpha) in plasma increased significantly at the start and up to 60 min after ischemia. No such increase was seen in animals with no spinal cord ischemia. Thus, free radical mediated and cyclooxygenase catalysed products of arachidonic acid are increased during spinal cord ischemia as a consequence of oxidative injury and inflammation.

Topics: Animals; Aorta, Thoracic; Biomarkers; Cerebrospinal Fluid; Dinoprost; F2-Isoprostanes; Free Radicals; Inflammation; Oxidation-Reduction; Reperfusion Injury; Spinal Cord; Spinal Cord Ischemia; Swine; Time Factors

Endotoxaemic challenge promptly causes lipid peroxidation. Porcine endotoxaemia can be used to replicate severe human septic shock. This model was used to evaluate non-enzymatic [8-Iso-prostaglandin F2alpha (8-Iso-PGF2alpha)] and enzymatic [15-keto-13,14-dihydro-prostaglandin F2alpha (15-K-DH-PGF2alpha)] lipid peroxidation, respectively, in relation to survival. The aim of this study was to correlate, if possible, pathophysiologic events during endotoxaemia to the levels of these arachidonic acid metabolites.. Nineteen pigs were anaesthetised, monitored (circulatory and respiratory variables in relation to lipid peroxidation) and given a continuous 6 h E. coli endotoxin (10 microg x kg(-1) x h(-1)) infusion. All animals were mechanically ventilated at constant tidal volumes and the inspired oxygen fraction was kept constant during the experimental period.. This endotoxin infusion caused expressed derangements in all pigs and death in 9 of them. The levels of 8-Iso-PGF2alpha, indicating oxidative injury, were different in time course, magnitude and fashion between survivors and non-survivors. The levels of 15-K-DH-PGF2alpha, indicating inflammatory response, showed a similar pattern. At 1 h the CO2 partial pressure in arterial blood was significantly higher in non-surviving pigs and correlated (r: 0.7; P<0.05) to the levels of 15-K-DH-PGF2alpha. Prostaglandin F2alpha is mainly metabolised in the lung. The lung weights were significantly (P<0.05) higher in non-surviving than in surviving animals. Both free radical and cyclooxygenase catalysed oxidative modification occurs during endotoxaemia.. Increased metabolism and inflammation, as evaluated by 15-K-DH-PGF2alpha, in the group of non-survivors may mediate the increase in arterial CO2. Thus, increased lipid peroxidation seems to be associated with endotoxaemic organ dysfunction and increased mortality.

Topics: Animals; Dinoprost; Endotoxemia; Female; Inflammation; Lipid Peroxidation; Male; Prostaglandins A; Swine; Time Factors

Two experiments were performed to investigate relationships between oxytocin, prostaglandin release, uterine emptying and fluid accumulation in the uterus. In Experiment 1, the effect of oxytocin on the pattern of prostaglandin release during uterine clearance of radiocolloid was measured in 5 normal mares and 5 mares with delayed uterine clearance. Uterine clearance was measured during estrus by scintigraphy at 0, 60 and 120 min after colloid infusion. After the 120-min reading, 20 IU, i.v., oxytocin were given, and the amount of colloid cleared was measured at 135, 150 and 180 min. Plasma was obtained prior to and during scintigraphy at 5- and 15-min intervals to measure concentrations of 15-keto-13,14-dihydro-PGF2 alpha metabolite (PGFM) by RIA. In Experiment 2, plasma PGFM levels were compared after administration of oxytocin in 8 normal mares and 6 mares with delayed uterine clearance to determine if intrauterine fluid stimulated prostaglandin release. Mares received 2 treatments in a cross-over design. Treatment 1 consisted of 20 IU, i.v., oxytocin during estrus. Treatment 2 consisted of an infusion of 10 mL, i.u., saline 15 min prior to oxytocin administration. Treatments were performed 4 to 6 h apart. Blood was collected and PGFM was measured as in experiment 1. Data were analyzed by least squares analysis of variance. In Experiment 1, regression analysis of scintigraphy and PGFM profiles indicated that time response curves differed between groups (P < 0.01). At 120 min, normal mares retained 40.4 +/- 4.9% (mean +/- SEM) of the radiocolloid while mares with delayed clearance retained 88 +/- 5%. Fifteen minutes after oxytocin administration (135 min), all normal mares and 4 of 5 mares with delayed clearance retained only < 6% of the colloid. During the first 120 min, plasma PGFM concentrations did not differ between the 2 groups. After oxytocin was given, plasma PGFM concentrations increased in 4 of 5 mares with delayed uterine clearance (80 to 3,096 pg/mL) but not in normal mares (13 to 46 pg/mL). In Experiment 2, plasma PGFM concentrations did not rise in normal mares but rose in 3 of 6 mares with delayed clearance (135 to 483 pg/mL) independent of treatment or period. The results suggest that intrauterine clearance of radiocolloid after oxytocin administration appears to be independent of PGF2 alpha release in normal mares during estrus. The difference in prostaglandin release response after oxytocin administration between the 2 groups was unrel

Topics: Animals; Cross-Over Studies; Dinoprost; Estrus; Female; Horses; Inflammation; Least-Squares Analysis; Oxytocin; Prostaglandins; Radioimmunoassay; Radionuclide Imaging; Reference Values; Regression Analysis; Streptococcus; Uterus

The metabolism of PGF2alpha in human and other species results initially in the formation of 15-keto-dihydro-PGF2alpha and later to several beta-oxidized metabolites, which are species-specific. Since the discovery of cyclooxygenase-2 (COX-2), the importance of measuring various arachidonic acid metabolites during inflammatory conditions is on focus. This study presents the development and validation of a new radioimmunoassay of 15-keto-dihydro-PGF2alpha as an index of lipid peroxidation via cyclooxygenase (COX-1 and COX-2) pathway. Furthermore, its application in endotoxin-induced acute inflammation in pigs is presented. An antibody was raised in rabbits by immunization with 15-keto-dihydro-PGF2alpha coupled to BSA at the carboxylic acid by 1,1'-carbonyldiimidazole method. The cross-reactivity of the antibody with PGF2alpha, 15-keto-PGF2alpha, PGE2, 15-keto-13,14-dihydro-PGE2, 8-iso-15-keto-13,14-dihydro-PGF2alpha, 11beta-PGF2alpha, 9beta-PGF2alpha, TXB2 and 8-iso-PGF3alpha was 0.02, 0.43, < 0.001, 0.5, 1.7, < 0.001, < 0.001, < 0.001, 0.01%, respectively. The intra-assay precision was 12.2% (CV) at the level of 64 pg/0.1 ml and 14.0% with 512 pg/0.1 ml in the human plasma. Similarly, intra-assay accuracy was 108.6% and 103.3% for the low and the high standards, respectively. The detection limit was about 45 pmol/L. 15-keto-dihydro-PGF2alpha levels in plasma from normal human volunteers were evaluated and found to correlate with the obtained values by GC-MS methods from other studies. The levels of 15-keto-dihydro-PGF2alpha in the plasma increased several-fold after endotoxin infusion (10 microg/kg/h over 6 h) to the pigs. Thus, this 1 5-keto-dihydro-PGF2alpha radioimmunoassay method is relevant to apply in inflammatory injury, and other physiological and pathophysiological studies, as an index of in vivo enzymatic lipid peroxidation.

Topics: Animals; Antibodies; Dinoprost; Female; Humans; Inflammation; Male; Predictive Value of Tests; Rabbits; Radioimmunoassay; Reference Values; Sensitivity and Specificity; Swine

This study investigates the plasma levels of 8-iso-PGF2alpha, a non-enzymatic, and 15-K-DH-PGF2alpha, a cyclooxygenase catalyzed oxidation product of arachidonic acid in an experimental porcine endotoxemic shock model. A significant (P < 0.001) and rapid appearance and disappearance of PGF2alpha metabolite after endotoxin infusion was very similar in both non-survival and survival groups indicating an acute progression and recession of inflammation. When oxidative injury was assessed by measuring free 8-iso-PGF2alpha the levels in plasma increased significantly up to 2 h and remained at this level until death among the non-survivors. This was apparently different from the survivors where the 8-iso-PGF2alpha levels increased to its height at 1 h, then decreased to the basal levels after 5 h. Thus, free radical and cyclooxygenase catalyzed oxidation of arachidonic acid occurs during endotoxemia. Free radical dependent oxidative injury following endotoxin induced inflammation may be the major cause of organ failure and increased mortality.

Topics: Animals; Arachidonic Acid; Biomarkers; Dinoprost; Endotoxemia; Escherichia coli Infections; F2-Isoprostanes; Female; Inflammation; Male; Oxidative Stress; Radioimmunoassay; Shock, Septic; Survival Analysis; Swine; Time Factors

An acute phase response was previously found in cows at parturition, which might be associated with uterine cytokine release. Five late pregnant cows were implanted with vascular catheters in both the maternal aorta and uterine vein. Blood samples were taken to study temporal relationships between changing plasma levels of proinflammatory cytokines and the periparturient acute phase response following prostaglandin (PG)-induced luteolysis at Day 275 of gestation. The plasma levels of three proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6), as well as progesterone (P4), PGFM and serum amyloid A (SAA) were measured every 4 h between PG induction and expulsion of the calf. In the arterial plasma, progesterone levels dropped to baseline levels within 10 h following PG treatment, indicative of complete luteolysis. Contrary to expectations, the uterine vein samples showed lower proinflammatory cytokine levels compared with the maternal aorta values. A classical acute phase response, as assessed by SAA, was observed during the expulsive stage, but not during luteolysis.

Topics: Animals; Apolipoproteins; Cattle; Corpus Luteum; Cytokines; Dinoprost; Female; Haptoglobins; Inflammation; Interleukin-1; Interleukin-6; Labor, Obstetric; Placenta; Pregnancy; Progesterone; Serum Amyloid A Protein; Tumor Necrosis Factor-alpha

Otitis media with effusion (OME) is a common middle ear inflammatory disease in the pediatric population. This article determines concentrations of three functionally and metabolically distinct inflammatory mediators in middle ear effusions (MEE) and corresponding plasma of children with OME. One hundred two patients (mean age, 4.9 years) with persistent OME were studied. Middle ear effusions were collected from all subjects and plasma from a subset at the time of tympanostomy tube insertion. Histamine was assayed radioisotopically, 13,14-dihydro-15-keto-prostaglandin F2 alpha (stable PGF2 alpha metabolite) by radioimmunoassay, and neutrophil chemotactic factor of anaphylaxis by modified Boyden chamber. Mean MEE levels of the mediators (39 +/- 13 ng/mL, 462 +/- 179 pg/mL, and 264% +/- 57% positive control, respectively) were markedly higher than those of corresponding plasma (0.5 +/- 0.1 ng/mL, 285 +/- 127 pg/mL, and 47% +/- 5% positive control, respectively). The mean histamine content of mucoid effusions (43.2 +/- 56.9 ng/mL) was significantly higher than that of purulent (22.5 +/- 10.5 ng/mL) and serous (17.9 +/- 16.8 ng/mL) effusions. Higher histamine levels were observed in effusions positive for Haemophilus influenzae when compared with those with other pathogenic isolates. The high concentrations of these mediators in MEE and their potential for inducing or sustaining the inflammatory process supports a role in the pathogenesis of OME.

Topics: Adolescent; Adult; Chemotactic Factors; Child; Child, Preschool; Chronic Disease; Dinoprost; Haemophilus influenzae; Histamine; Humans; Infant; Inflammation; Interleukin-8; Otitis Media with Effusion; Prostaglandins F