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Pediatric Research Oct 1994Cyclooxygenase products are metabolized by omega-oxidation as well as beta-oxidation. Children with Zellweger syndrome (ZS) are characterized by peroxisome deficiency.... (Clinical Trial)
Clinical Trial Comparative Study
Cyclooxygenase products are metabolized by omega-oxidation as well as beta-oxidation. Children with Zellweger syndrome (ZS) are characterized by peroxisome deficiency. To evaluate the role of peroxisomal beta-oxidation on cyclooxygenase metabolites, the degradation of endogenous prostaglandin (PG) E2, prostacyclin, and thromboxane (Tx) A2 was assessed in children with ZS (n = 7) and in healthy children (n = 7). PGE2, prostacyclin, TxB2, and their major urinary metabolites 7 alpha-hydroxy-5,11-dioxo-tetranor-prosta-1,16-dioic acid, 2,3-dinor-6-oxo-PGF1 alpha, and 2,3-dinor-TxB2, respectively, were measured in urine by gas chromatography-mass spectrometry/mass spectrometry. The median excretion of healthy children was 17.9 ng of 7 alpha-hydroxy-5,11-dioxo-tetranor-prosta-1,16-dioic acid/mg creatinine (interquartile range, 6.3 to 19.4 ng/mg), 0.38 ng of 2,3-dinor-6-oxo-PGF1 alpha/mg creatinine (interquartile range, 0.34 to 0.70 ng/mg), and 0.36 ng of 2,3-dinor-TxB2/mg creatinine (interquartile range, 0.14 to 0.54 ng/mg). In contrast, none of these metabolites could be detected in urine of children with ZS (p < 0.002). However, we identified in the urine of these children a new metabolite of PGE2 as 11-hydroxy-9,15-dioxo-prost-5-en-1,20-dioic acid by gas chromatography-mass spectrometry, and we confirmed the presence of 9,11-dihydroxy-15-oxo-prost-5-en-1,20-dioic acid the main urinary metabolite of PGF2 alpha in ZS. Importantly, these two metabolites were only detectable in urine of children with ZS.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Biotransformation; Child; Dinoprostone; Epoprostenol; Female; Gas Chromatography-Mass Spectrometry; Humans; Male; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Reference Values; Thromboxane B2; Zellweger Syndrome
PubMed: 7816519
DOI: 10.1203/00006450-199410000-00006 -
Fundamental & Clinical Pharmacology 2000Numerous pathological conditions are suspected to involve free radical production as part of their pathogenic process. Therefore, a pharmacological control of oxidative... (Review)
Review
Numerous pathological conditions are suspected to involve free radical production as part of their pathogenic process. Therefore, a pharmacological control of oxidative stress could probably benefit many vascular, inflammatory or degenerative diseases. However, the development of antioxidant drugs and their clinical evaluation are limited by the absence of an accurate, reliable and easy-to-handle marker of tissue oxidative events. Isoprostanes (isoPs), a prostaglandin-related series of metabolites, are emerging as major candidates for clinical measurement of oxidative stress. They are chemically stable products of lipid peroxidation, formed in cellular membranes and subsequently released and excreted in the urine. Many recent clinical studies have reported that urinary and plasma levels of isoPs (in particular the iPF2alpha-III isomer also called 8-epi-PGF2alpha) are increased in clinical conditions where oxidative stress is suspected to play a pathogenic role. Moreover, isoPs have been detected in tissue extracts from atherosclerotic plaques and Alzheimer patients brain tissue. Finally, antioxidant treatments such as vitamin E supplementation appear to reduce isoPs levels in biological fluids of treated patients. These preliminary observations argue for a further investigation of isoPs as a practical pharmacodynamic endpoint for the clinical evaluation of antioxidant therapies.
Topics: Antioxidants; Biomarkers; Humans; Oxidative Stress; Prostaglandins; Stereoisomerism
PubMed: 10681068
DOI: 10.1111/j.1472-8206.2000.tb00387.x -
Canadian Journal of Physiology and... Jun 2017We investigated the effect of the major inflammatory cytokine interleukin-1beta (IL-1β) on the ventilatory response to hypoxia. The goal was to test the hypothesis that...
We investigated the effect of the major inflammatory cytokine interleukin-1beta (IL-1β) on the ventilatory response to hypoxia. The goal was to test the hypothesis that IL-1β impairs the hypoxic ventilatory response in vivo by indirectly inhibiting respiratory neurons in the brainstem via prostaglandins. Thus, IL-1β was delivered by cerebroventricular injection, and the ventilatory hypoxic response was assessed in anesthetized, spontaneously breathing rats pretreated with or without diclofenac, a nonspecific inhibitor of prostaglandin synthesis. We found that the slope of the ventilatory response to hypoxia decreased almost 2-fold from 10.4 ± 3.02 to 4.06 ± 0.86 mL·min·(mm Hg) (-61%) 90 min after administration of IL-1β (p < 0.05). The slope of tidal volume and mean inspiratory flow also decreased from 0.074 ± 0.02 to 0.039 ± 0.01 mL·(mm Hg) (-45%, p < 0.05), and from 0.36 ± 0.07 to 0.2 ± 0.04 mL·s·(mm Hg) (-46%, p < 0.05), respectively. Pretreatment with diclofenac blocked these effects. Thus, the data indicate that IL-1β degrades the ventilatory hypoxic response by stimulating production of prostaglandin. The increase of cerebral levels of IL-1β, which is induced by the activation of immune cells in the brain, may impair respiratory chemoreflexes.
Topics: Animals; Diclofenac; Dose-Response Relationship, Drug; Drug Interactions; Humans; Hypoxia; Interleukin-1beta; Prostaglandins; Pulmonary Ventilation; Rats; Respiration
PubMed: 28177673
DOI: 10.1139/cjpp-2016-0419 -
Journal of Molecular and Cellular... Aug 1975
Review
Topics: 8,11,14-Eicosatrienoic Acid; Adenosine Monophosphate; Animals; Arachidonic Acids; Arrhythmias, Cardiac; Coronary Vessels; Depression, Chemical; Glucose; Heart; Oxygen Consumption; Palmitic Acids; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostaglandins A; Prostaglandins E; Prostaglandins F; Stimulation, Chemical; Sympathetic Nervous System; Synaptic Transmission
PubMed: 167180
DOI: 10.1016/0022-2828(75)90112-1 -
The American Journal of Physiology Dec 1987Tritium-labeled prostaglandin F2 alpha was administered via orogastric tube to bile duct-cannulated suckling and weanling rats to determine if maturational differences...
Tritium-labeled prostaglandin F2 alpha was administered via orogastric tube to bile duct-cannulated suckling and weanling rats to determine if maturational differences were present in the biliary excretion of prostaglandin F2 alpha and metabolites. Animals were killed 2 h after radioactivity administration. Characterization of radioactivity present in bile revealed age-related differences in biliary prostaglandin F2 alpha excretion. Suckling rats had a greater proportion of radioactivity migrating in chromatographic regions of greater polarity than prostaglandin F2 alpha. Compared with the weanling, a significantly greater amount of radioactivity cochromatographed with intact, unmetabolized prostaglandin F2 alpha (33.08 +/- 1.99 vs. 21.38 +/- 1.46). These results indicate that orogastrically administered prostaglandin F2 alpha can be absorbed from the gastrointestinal tract, transported to the liver, and subsequently excreted into bile and detected in an unmetabolized form in suckling and weanling rats. The enterohepatic circulation of milk-derived prostaglandin present in bile may contribute to the overall content of intestinal prostaglandins.
Topics: Age Factors; Animals; Animals, Suckling; Bile; Dinoprost; Intestinal Absorption; Intubation, Gastrointestinal; Liver; Prostaglandins F; Rats
PubMed: 3480694
DOI: 10.1152/ajpgi.1987.253.6.G787 -
Annales de Dermatologie Et de... 1980The biosynthesis of prostaglandins E2 (PGE2) and F2 alpha (PGF2) from exogenous arachidonic acid (AA) was investigated in 12 involved and uninvolved psoriatic epidermis... (Comparative Study)
Comparative Study Review
The biosynthesis of prostaglandins E2 (PGE2) and F2 alpha (PGF2) from exogenous arachidonic acid (AA) was investigated in 12 involved and uninvolved psoriatic epidermis and in 6 normal epidermis. PGE2 and PGF2 were determined by radio-immuno-assay after addition of 25 microgram of AA and 1 hour incubation. The biosynthesis of PGE2 and PGF2 alpha was higher in psoriatic epidermis than in control epidermis but lower in involved than in uninvolved epidermis. The ratio PGE2/PGF2 alpha is decreased in involved epidermis when compared with uninvolved epidermis and with controls. These quantitative and qualitative disturbances of the PG metabolism in psoriatic epidermis might play an important role in the pathogenesis of the disease. They could be responsible for abnormal keratinocyte differentiation and proliferation, lipid membrane abnormalities and abnormal immune response of psoriatic patients.
Topics: Epidermis; Humans; Lipid Metabolism; Prostaglandins E; Psoriasis
PubMed: 7015965
DOI: No ID Found -
Acta Paediatrica (Oslo, Norway : 1992) Jan 2018The metabolic changes that occur during the postnatal weaning period appear to be particularly important for future health, and breast milk is considered to provide the...
AIM
The metabolic changes that occur during the postnatal weaning period appear to be particularly important for future health, and breast milk is considered to provide the optimal source of infant nutrition. This pilot study from September 2013 to May 2015 examined the effect of breastfeeding on prostaglandin metabolism in healthy term infants.
METHODS
Urine samples were collected from 19 infants at one month of age in the Juntendo University Hospital, Tokyo, Japan. The 13 infants in the breast-fed group received less than 540 mL/week of their intake from formula, and the other six were exclusively fed on formula. At six months, we sampled 14 infants: nine breast-fed and five receiving formula. The infants were from normal single pregnancies and free from perinatal complications. We analysed urinary prostaglandin metabolites-tetranor prostaglandin E metabolite (t-PGEM) and tetranor prostaglandin D metabolite (t-PGDM)-using liquid chromatography tandem-mass spectrometry.
RESULTS
Urinary t-PGDM excretion at one and six months was significantly lower in breast-fed infants than formula-fed infants. However, urinary t-PGEM excretion at one and six months was not significantly different between the groups.
CONCLUSION
Our study showed that the type of feeding in early infancy affected prostaglandin metabolism in healthy term infants.
Topics: Breast Feeding; Female; Humans; Infant; Lipid Metabolism; Male; Pilot Projects; Prostaglandin D2; Prostaglandins
PubMed: 28898456
DOI: 10.1111/apa.14068 -
Biochemistry International Feb 1988Arachidonic acid (5 microM), prostaglandin E2 (0.28 microM) and F2 alpha (14 microM) inhibited (P less than 0.01) the rates of net leucine transamination, leucine...
Arachidonic acid (5 microM), prostaglandin E2 (0.28 microM) and F2 alpha (14 microM) inhibited (P less than 0.01) the rates of net leucine transamination, leucine oxidative decarboxylation and total CO2 production from leucine in extensor digitorum communis muscles from fed ten-day-old chicks. Indomethacin (50 microM) markedly inhibited (P less than 0.01) the rate of PGE2 production in the presence of 5 microM arachidonic acid and prevented the inhibition of leucine degradation by arachidonic acid in skeletal muscle. These results demonstrate that the actions of arachidonic acid on leucine degradation in chick skeletal muscle are mediated by metabolites generated via the cyclooxygenase pathway and that prostaglandins may play a role in the regulation of leucine degradation in skeletal muscle.
Topics: Animals; Arachidonic Acid; Arachidonic Acids; Chickens; Dinoprost; Dinoprostone; Indomethacin; Leucine; Muscles; Prostaglandins E; Prostaglandins E, Synthetic; Prostaglandins F
PubMed: 3130060
DOI: No ID Found -
Life Sciences Nov 1982
Topics: Animals; Antibody Specificity; Brain; Brain Chemistry; Indomethacin; Male; Microwaves; Pituitary Gland; Prostaglandin D2; Prostaglandins; Prostaglandins D; Radioimmunoassay; Rats; Rats, Inbred Strains; Spinal Cord; Tissue Distribution
PubMed: 6960222
DOI: 10.1016/0024-3205(82)90101-1 -
Arzneimittel-Forschung Nov 1997Prostaglandin research has led to a plethora of discoveries on pathophysiology. Remarkable examples are arteriosclerosis and its complications, where the role of... (Review)
Review
Prostaglandin research has led to a plethora of discoveries on pathophysiology. Remarkable examples are arteriosclerosis and its complications, where the role of thromboxane and prostacyclin was discovered and led to the development of strategies for the prevention of myocardial infarction by acetylsalicylic acid. Nephrology has gained new insights into the role of prostaglandins in kidney function under physiological and pathological conditions. The action of various drugs on kidney function has led to the understanding of interactions between non-steroidal antiinflammatory drugs and antihypertensive drugs and lithium. Systematic research on the role of prostaglandins and leukotrienes in inflammation and in asthma has led to the development of new drugs for both diseases. The original idea to use prostaglandins themselves for various indications has not been realized. As observed often in the past in biological and technological research the most important discoveries came unexpected and as a surprise to the specialists: The use of acetylsalicylic acid for primary and secondary prevention of myocardial infarction and the development of a new generation of non-steroidal antiinflammatory drugs with much better gastrointestinal and renal tolerance.
Topics: Animals; Heart Diseases; Humans; Prostaglandin Antagonists; Prostaglandins
PubMed: 9463305
DOI: No ID Found