6-ketoprostaglandin-f1-alpha and Alcoholism

The objective of this project has been to develop a sensitive and specific assay for prostaglandins in human cerebrospinal fluid (CSF) from patients with alcoholism and appropriate controls using gas chromatography/mass spectrometry. This study was initiated because numerous literature reports strongly suggest that a relationship exists between ethanol's central nervous system effects and the central production of prostaglandins. In both human and animal studies, administration of prostaglandin synthesis inhibitors prior to administration of ethanol attenuated central nervous system effects of ethanol. Samples from alcoholics after a three week period of abstinence and normals contained none of the measured prostaglandins (PGE2, PGE1, PGF1a, PGF2a, 6-keto-PGF1a) at a concentration more than twice the limit of quantification (3 pg/mL CSF). Comparison of GC/MS and radioimmunoassay methods provided further validation for these results. Literature reports of much higher levels of prostaglandins in normal controls, i.e., tens to hundreds of pg/mL CSF, appear to be incorrect. Examination of monkey CSF provided a positive control, since several of the prostaglandins were easily quantifiable in these samples.

Topics: 6-Ketoprostaglandin F1 alpha; Alcoholism; Animals; Dinoprost; Dinoprostone; Gas Chromatography-Mass Spectrometry; Humans; Macaca mulatta; Prostaglandins; Radioimmunoassay

To study the effect of maternal ethanol consumption on the production of prostacyclin and thromboxane, we measured urinary 6-keto-prostaglandin F1 alpha (a hydration product of prostacyclin), 2,3-dinor-6-keto-prostaglandin F1 alpha (generated from 6-keto-prostaglandin F1 alpha through beta oxidation), and thromboxane B2 (a hydration product of thromboxane A2) using consequent high-performance liquid chromatography and radioimmunoassays in 39 drinking women and 16 abstinent controls, and in their infants. Thirty-one drinkers and two control women smoked. Maternal ethanol consumption was accompanied by increased output of prostacyclin and thromboxane metabolites in the mothers, but no relationship was apparent between the increased metabolites and development of fetal alcohol effects in 22 mothers. There were no differences between smoking and nonsmoking drinkers in the excretion of these prostanoids. All the infants born to the drinkers had increased thromboxane B2 excretion, but the excretion of prostacyclin metabolites was increased only in infants with fetal alcohol effects. The ratio between prostacyclin and thromboxane was reduced in infants with fetal alcohol effects. Thus, maternal ethanol consumption is associated with enhanced prostacyclin and thromboxane synthesis, perhaps in the kidneys and/or systemic circulation and vascular bed. Similar changes may also occur in the fetus and/or newborn with fetal alcohol effects.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Alcoholism; Epoprostenol; Female; Fetal Alcohol Spectrum Disorders; Humans; Pregnancy; Pregnancy Complications; Temperance; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Acetaldehyde; Acetates; Alcohol Drinking; Alcoholism; Animals; Aorta; Arachidonic Acid; Arachidonic Acids; Ethanol; In Vitro Techniques; Kinetics; Lipoproteins, HDL; Male; Muscle, Smooth, Vascular; Prostaglandin Endoperoxides; Prostaglandins H; Rats; Rats, Inbred Strains

1. The rates of secretion into the circulation of prostaglandin E, prostacyclin, and thromboxane A2 were estimated in male alcoholics on the third day of withdrawal and in control subjects by measuring appropriate metabolites in urine. 2. Urinary levels of tetranor-5,11-diketo-7 alpha-hydroxyprostane-1,16-dioic acid (the major urinary metabolite of prostaglandins E1 and E2), of 2,3-dinor-6-keto-prostaglandin F1 alpha (the major urinary metabolite of prostacyclin) and of 6-keto-prostaglandin F1 alpha (the stable hydrolysis product of prostacyclin) were significantly different from the normal subjects in the alcoholic group. In contrast, 2,3-dinor-thromboxane B2 (the major urinary metabolite of thromboxane A2) and thromboxane B2 (the stable hydrolysis product of thromboxane A2) were not significantly different between the groups. 3. These data suggest that the ratio of the vasodilator prostanoids prostaglandin E and prostacyclin and the vasoconstrictor prostanoid thromboxane A2 is lower than in normal subjects, in alcoholics during withdrawal. This may be one causal factor for the higher incidence of hypertension observed in withdrawing alcoholics compared with control subjects.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Alcoholism; Epoprostenol; Ethanol; Humans; Male; Middle Aged; Prostaglandins E; Prostanoic Acids; Substance Withdrawal Syndrome; Thromboxane B2; Thromboxanes

The excretion of 2,3-dinor-6-keto prostaglandin F1 alpha, a major urinary metabolite of prostacyclin, and the formation of thromboxane B2, a stable metabolite of thromboxane A2, by platelets stimulated by adenosine diphosphate, were studied in alcoholics, who had been admitted for detoxification. Once prolonged heavy drinking had stopped, platelet count and thromboxane formation, calculated either per 10(7) platelets or per litre of blood, significantly increased (p less than 0.05), while the skin bleeding time and urinary excretion of the metabolite of prostacyclin decreased (p less than 0.05). The balance between prostacyclin and thromboxane therefore seemed to favour the excretion of prostacyclin while it shifted to favour thromboxane formation about a week later.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Alcoholism; Bleeding Time; Blood Platelets; Humans; Male; Middle Aged; Platelet Count; Substance Withdrawal Syndrome; Thromboxane B2; Time Factors