Urinary 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin-F1α in healthy post-menopausal and pre-menopausal women receiving aspirin 100 mg.

The prevalence of cardiovascular diseases in women increases sharply after menopause. In postmenopausal women, thromboxane production increases while prostacyclin decreases. Low dose aspirin reduces the production of both thromboxane and prostacyclin. The present study was an open-label clinical trial with two parallel groups of 15 premenopausal women and 15 postmenopausal women. Twenty-four hours urine was collected from each subject before and after aspirin 100 mg daily for 7 days. The concentration of thromboxane and prostacyclin was measured as their metabolites (11-dehydro-thromboxane B(2) and 2,3-dinor-6-keto-prostaglandin-F(1α)) in urine using enzyme immunoassay methods. This study showed that aspirin significantly reduced thromboxane in both groups with significantly larger percentage reduction in postmenopausal women compared to premenopausal women (73.32 vs. 61.13%, p = 0.021). This study also showed that aspirin reduced prostacyclin significantly in both groups, but the percentage reduction between the groups was not significantly different. The decrease in the ratio of 11-dTXB(2)/2,3-dinor-6-keto-PGF(1α) should be compared to assess aspirin efficacy as an antithrombotic. Calculation of the ratio of 11-dTXB(2)/2,3-dinor-6-keto-PGF(1α) before aspirin consumption was higher in postmenopausal women than in premenopausal women. The decrease in 11-dTXB(2)/2,3-dinor-6-keto-PGF(1α) ratio by aspirin was greater in postmenopausal women than in premenopausal women (1.91 vs. 0.17; p = 0.022). It was concluded that aspirin reduced thromboxane and prostacyclin significantly in each group with significant 11-dTXB(2) percentage reduction between groups and non-significant 2,3-dinor-6-keto-PGF(1α) percentage reduction between groups, but reduced the 11-dTXB(2)/2,3-dinor-6-keto-PGF(1α) ratio much larger in postmenopausal women compared to that in premenopausal women.

Disposition and metabolism of a novel prostanoid antiglaucoma medication, tafluprost, following ocular administration to rats.

The disposition and metabolism of tafluprost, an ester prodrug of the 15,15-difluoro-prostaglandin F(2alpha) antiglaucoma agent, have been studied in rats after ocular administration. Radioactivity was absorbed very rapidly into the eye and systemic circulation after a single ocular dose of 0.005% [(3)H]tafluprost ophthalmic solution, with maximum levels in plasma and most eye tissues occurring within 15 min. The absorption ratio of radioactivity was approximately 75%, suggesting the high availability of ocular administration of tafluprost. Approximately 10% of the dose was present in cornea at this time, and radioactivity concentrations in this tissue exceeded those in aqueous humor and iris/ciliary body throughout the 24-h study period. After repeated daily ocular doses, radioactivity levels remained greatest in cornea, followed by iris/ciliary body that replaced aqueous humor as the eye tissue containing the second highest radioactivity concentration. In female rats, radioactivity was excreted equally between urine and feces after a single ocular dose, whereas in male rats more was excreted in feces, reflecting the greater biliary excretion in males rats (50% dose) compared with females rats (33% dose). Tafluprost was extensively metabolized in the rat, such that intact prodrug was not detected in plasma, tissues, or excreta by radio-high-performance liquid chromatography. On the other hand, the active moiety, tafluprost acid, was the only noteworthy radioactive component in cornea, aqueous humor, and iris/ciliary body for at least 8 h after the ocular dose, and it was also a major plasma metabolite in early time points. The gender differences in conjugation reactions resulted in the differences in the excretion.

Increased urinary F(2)-isoprostanes levels in the patients with Alzheimer's disease.

Isoprostanes, novel markers of oxidative injury, are generated by the free radical-mediated peroxidation of arachidonic acid (AA). They are thought to be important in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). Using gas chromatography-mass spectrometry (GC-MS), we investigated the alteration of urinary F(2)-isoprostanes in AD patients compared to that of healthy subjects. Our results show that the levels of urinary F(2)-isoprostanes, sum of the prostaglandin F(2 alpha) isomer; prostaglandin F(2 alpha) (PGF(2 alpha)), prostaglandin F(2 beta) (PGF(2 beta)), and 8-isoprostaglandin F(2 alpha) (8-isoPGF(2 alpha)), significantly increased in AD patients (P < 0.05). The concentration of urinary 8-isoPGF(2 alpha), one of the biomarkers of oxidative stress, was not significantly different between 34 AD patients and 20 age-matched controls (P > 0.05). The PGF(2 alpha), formed by endoperoxide reductase from PGH(2), was significantly increased in AD patients, when compared with the levels of the normal controls (P < 0.05). The PGF(2 alpha), an enzymatic product of arachidonic acid, may affect the pathogenesis of AD. In addition, urinary F(2)-isoprostanes can play an important role as a biomarker in AD.

[Comparative morpho-functional assessment of the impact produced by prolonged infusions of prostaglandins E and F on the course of genetically preconditioned arterial hypertension]. / Sravnitel'naia morfofunktsional'naia otsenka vliianiia prolongirovannykh infuzii prostaglandinov E i F na techenie geneticheski obuslovlennoi arterial'noi gipertonii.

The administration of prolonged intravenous infusions of prostaglandins is defined; the method provided for specifying a long-term impact produced by prostaglandins on a nature of the course of genetically preconditioned arterial hypertension (AHT) in rats. Infusions of PGE-2 bring about a prolonged and stable reduction of mean arterial presser (AP) by 10% versus its original value; they intensify 2-fold the depressor baroreflectory regulation and stimulate the urinary excretion of endogenous renal PGF-2 alpha; besides, they contribute to a better blood supply to organs, i.e. an increased perfusion of the cortical and medullary layers of the kidneys and of the brain substances; and dilatation of the intramural branches of the coronary arteries, due to which the AP becomes milder. Infusions of PGF-2 alpha contribute to a prolonged and stable elevation of mean AP by 12% versus the original value; they inhibit the depressor baroreflectory regulation and intensify the pressor baroreflectory regulation; they, additionally, induce the urinary excretion of endogenous renal PGF-2 alpha and correct the lesions in the blood supply to organs, i.e. pathological microcirculation, anemia and spasm of the renal parenchyma, ischemic foci in the myocardium, spastic contraction of small cerebral arteries, edema and destructive changes (of the local necrosis variation) in the cerebral substance microvessels concomitant with a commencing diapedetic hemorrhages. Finally, all above listed lesions are signs of the malignant AP course.

Effects of exogenous heme on renal function: role of heme oxygenase and cyclooxygenase.

We examined the effects of heme administration (15 mg/kg IV) on indexes of renal carbon monoxide production and contrasted the renal functional response to heme in anesthetized rats pretreated and not pretreated with stannous mesoporphyrin (40 micromol/kg IV) to inhibit heme oxygenase or sodium meclofenamate (5 mg/kg IV plus infusion at 10 microg/kg per minute) to inhibit cyclooxygenase. In rats without drug pretreatment, heme administration decreased renal vascular resistance and increased renal blood flow, urine volume, and sodium excretion associated with augmented urinary excretion of 6-keto-PGF1alpha and enhanced concentration of carbon monoxide in the renal cortical microdialysate. Pretreatment with stannous mesoporphyrin did not prevent heme from producing renal vasodilation and increasing renal blood flow but abolished the diuretic and natriuretic responses. Conversely, pretreatment with sodium meclofenamate blunted the renal vasodilatory effect of heme but affected neither the diuretic nor the natriuretic effect. We conclude that heme-induced renal vasodilation is a cyclooxygenase-dependent response involving increased synthesis of PGI2, whereas heme-induced diuresis and natriuresis are heme oxygenase-dependent responses involving inhibition of tubular reabsorption of sodium and water through undefined mechanisms.

Dietary fish protein lowers blood pressure and alters tissue polyunsaturated fatty acid composition in spontaneously hypertensive rats.

OBJECTIVE: To investigate the effect of two types of dietary protein on blood pressure, liver fatty acid desaturation and composition, and urine 6-keto-prostaglandin-F (PGF(1alpha)) level, the metabolite of prostacyclin. METHODS: 5-wk-old spontaneously hypertensive rats were fed 20% casein or purified fish protein. The fat source was 5% ISIO oil, which contains 47.9% (omega-6) and 1.7% (omega-3) total polyunsaturated fatty acids. After 2 mo on the diet, systolic blood pressure was reduced with fish protein compared with casein (189.8 +/- 10.5 versus 220.7 +/- 8.7). RESULTS: Excretion of 6-keto-PGF(1alpha) in urine was negatively correlated with blood pressure. Liver cholesterol and phospholipid concentrations were 1.71- and 1.27-fold lower with fish protein than with casein, respectively. The fish protein diet lowered the 20:4(omega-6) proportion and the ratio of 20:4(omega-6) to 18:2(omega-6) in liver microsomal lipids and phospholipids, which was due to the reduced microsomal Delta6(omega-6) desaturation activity. Dietary protein source did not affect omega-3 fatty acid composition, and this was associated with a similar activation of Delta6(omega-3) desaturation in liver microsomes. CONCLUSIONS: The present data indicated a significant blood pressure-lowering effect caused by fish protein, rather than by casein, that modified the fatty acid composition of liver phospholipids and liver microsomal total lipids.

Urinary F2-isoprostanes formation in kidney transplantation.

BACKGROUND: Oxygen free-radical mediated lipid peroxidation has been implicated in many diseases such as chronic renal failure, hemodialysis and chronic kidney transplant rejection. However, insight into the role of free radical generation in kidney transplantation has been constrained by the limitations of current indexes of oxidant stress in vivo. Isoprostaglandin F2alpha type-III (iPF2alpha-III, formerly known as 8-iso-prostaglandin F2alpha) is emerging as a reliable marker of oxidant stress in vivo. The purpose of our study was to investigate iPF2alpha-III formation as an index of lipid peroxidation in the 5 d following kidney transplantation. METHODS: Urinary iPF2alpha-III measurements were performed by enzyme immunoassay from day I to 5 in 11 patients undergoing kidney transplantation. Results were compared with 11 healthy volunteers matched in sex, age and cigarette smoking. RESULTS: Urinary excretion of iPF2alpha-III at day 1 did not significantly differ between control and transplant group (111 +/- 17 vs. 92 +/- 10 pM/ mM creatinine, respectively, NS). Urinary iPF2alpha-III levels did not differ between day 1 to 5, and were not correlated to cold ischaemia time. CONCLUSION: Our study shows no evidence of enhanced lipid peroxidation in the first 5 d following kidney transplantation.

Eicosanoid production, thrombogenic ratio, and serum and LDL peroxides in normo- and hypercholesterolaemic post-menopausal women consuming two oleic acid-rich diets with different content of minor components.

The present paper compares the effects of two monounsaturated oils, extra virgin olive oil (EVOO) and high-oleic acid sunflower oil (HOSO), on serum and LDL peroxides, eicosanoid production and the thrombogenic ratio (thromboxane (TX) B2:6-keto-prostaglandin F1alpha) in fourteen non-obese post-menopausal women. The subjects, mean age 63 (SD 11) years, were assigned to two consecutive oleic acid-rich 28 d dietary periods. EVOO and HOSO represented 62 % of the total lipid intake and were used as the only culinary fat during the first and second dietary periods respectively. Serum peroxides, plasma alpha-tocopherol and TXB2 levels in stimulated platelet-rich plasma (PRP-TXB2) were significantly higher (P < 0.01, P < 0.001, and P < 0.05, respectively) after the HOSO diet than after the EVOO diet. The relationship between the serum cholesterol level (< 6.21 mmol/l or > or = 6.21 mmol/l) and the type of dietary oil on eicosanoids, peroxides and alpha-tocopherol were evaluated by two-way ANOVA. Dietary oil significantly affected (P < 0.05) the PRP-TXB2 level, whereas serum and LDL peroxides were significantly affected (P < 0.001 and P < 0.01, respectively) by the serum cholesterol level. The plasma alpha-tocopherol level was significantly affected by the serum cholesterol level and the type of dietary oil (both P < 0.001). No significant relationships were found between serum cholesterol levels, serum peroxide or LDL peroxide levels, plasma alpha-tocopherol concentrations or alpha-tocopherol intakes with eicosanoid production or the thrombogenic ratio due to dietary changes. However, in spite of their higher alpha-tocopherol levels, hypercholesterolaemic subjects showed increased peroxidation in serum and LDL in comparison with normocholesterolaemic subjects on the HOSO diet in comparison with the EVOO diet. These findings suggest that differences in the type of minor compounds, as well as in the concentration of linoleic acid, in both these monounsaturated oils may play an important role in modulating eicosanoid production and lipoprotein peroxidation when they constitute a large proportion of the diet of post-menopausal women.

Endogenous biosynthesis of thromboxane and prostacyclin in 2 distinct murine models of atherosclerosis.

Thromboxane A(2) is a potent vasoconstrictor and platelet agonist; prostacyclin is a potent platelet inhibitor and vasodilator. Altered biosynthesis of these eicosanoids is a feature of human hypercholesterolemia and atherosclerosis. This study examined whether in 2 murine models of atherosclerosis their levels are increased and correlated with the evolution of the disease. Urinary 2,3-dinor thromboxane B(2) and 2,3-dinor-6-keto prostaglandin F(1 alpha), metabolites of thromboxane and prostacyclin, respectively, were assayed in apoliprotein E (apoE)-deficient mice on chow and low-density lipoprotein receptor (LDLR)-deficient mice on chow and a Western-type diet. Atherosclerosis lesion area was measured by en face method. Both eicosanoids increased in apoE-deficient mice on chow and in LDLR-deficient mice on a high-fat diet, but not in LDLR-deficient mice on chow by the end of the study. Aspirin suppressed ex vivo platelet aggregation, serum thromboxane B(2), and 2,3-dinor thromboxane B(2), and significantly reduced the excretion of 2,3-dinor-6-keto prostaglandin F(1 alpha) in these animals. This study demonstrates that thromboxane as well as prostacyclin biosynthesis is increased in 2 murine models of atherogenesis and is secondary to increased in vivo platelet activation. Assessment of their generation in these models may afford the basis for future studies on the functional role of these eicosanoids in the evolution and progression of atherosclerosis. (Blood. 2000;96:3823-3826)

Covalent protein adducts of hydroquinone in tissues from rats: quantitation of sulfhydryl-bound forms following single gavage or intraperitoneal administration or repetitive gavage administration.

The current studies were conducted to investigate the degree and type of protein binding of hydroquinone (HQ) in the rat following single oral or intraperitoneal (ip) or repeated oral administrations. Male or female F-344 rats or male SD rats received a single dose of HQ at 0, 25, 50, or 100 mg/kg by either gavage or ip injection (SD rats only). In addition, male or female F-344 or male SD rats received HQ by gavage for 6 weeks (5 days/week) at 0, 25, or 50 mg/kg/day. Sulfhydryl-bound HQ was quantitated in protein from blood, kidneys, livers, or spleens 24 h after treatment using an alkaline permethylation procedure. The amount of total protein-S adducts increased with increasing dose in all the tissues that were assayed. Female rats had higher levels of adducts in blood, livers, and kidneys than did male rats when they were treated orally. Male F-344 rats treated orally had elevated levels of adducts in these same tissues compared to SD rats treated orally. For all genders and strains of rats and for all treatment regimens, mono-adducts predominated in livers (>72% of total). In the kidneys, tri- and tetrasubstituted adducts predominated with the summation accounting for >60% of the total. Ip administration of HQ resulted in significantly elevated levels of adducts in all the tissues that were examined, with the greatest increases seen for protein from blood and spleens. Levels of protein-S adducts of HQ in rat kidney following a single gavage administration correlated well with previously published differences in acute HQ nephrotoxicity in rats (female F-344 rat > male F-344 rat > male SD rat). Elevated levels of HQ protein-S adducts following repeated gavage administration did not correlate to measurable clinical signs of nephrotoxicity. Evidence is presented suggesting a possible role for the prostaglandin H synthase complex in the metabolic activation of HQ. In addition, protein arylation alone cannot account for the greater sensitivity of male F-344 rats toward chronic administration of HQ. The sensitivity of male F-344 rats to HQ is likely due to other factors, including the incidence and severity of chronic progressive nephropathy.

Monitoring of the thromboxane A2/prostacyclin ratio in the urine of patients with retinal vascular occlusion through the low-dose-aspirin therapy using the gas chromatography/selected ion monitoring method.

We determined the levels of the stable urinary metabolites of thromboxane A2 and prostacyclin, 11-dehydro-thromboxane B2 (11-dehydro-TXB2) and 2,3-dinor-6-keto-prostaglandin F1alpha (2,3-dinor-6-keto-PGF1alpha) in patients with retinal vascular occlusion (RVO) to elucidate the change of the thromboxane A2/prostacyclin (TX/PGI) ratio with this disease and the effect of low-dose-aspirin therapy. 11-Dehydro-TXB2 and 2,3-dinor-6-keto-PGF1alpha were converted to 1-methyl ester-propylamide-9,12,15-tris-dimethylisopropylsilyl ether derivative and 1-methyl ester-6-methoxime-9,12,15-tris-dimethylisopropylsilyl ether derivative, respectively, and applied to a gas chromatography/selected ion monitoring. The average level of 11-dehydro-TXB2 in 30 patients with RVO was 1038 +/- 958 pg/mg creatinine. It was significantly higher than that of 27 healthy volunteers, which was 616 +/- 294 pg/mg creatinine (p < 0.05 with unpaired t-test). However, 2,3-dinor-6-keto-PGF1alpha levels were not significantly different between these two groups. The average ratio of TX/PGI in the RVO patients was 32 +/- 26 and it was significantly higher than that of healthy volunteers, 17 +/- 10 (p < 0.01). Patients with central retinal artery occlusion or branch retinal artery occlusion showed greatly high 11-dehydro-TXB2 levels and TX/PGI ratios, although the number of patients was limited in the current study. After the administration of low-dose aspirin (40 mg/day) for about 1 month, the TX/PGI ratio decreased to around the normal level. Following the levels for up to 10 months, they also remained at the normal level. These observations suggested that the 11-dehydro-TXB2 levels and the TX/PGI ratio reflect the pathological conditions of RVO and are useful markers of the treatment.

Urinary thromboxane A2/prostacyclin balance reflects the pathological state of a diabetic.

Levels of the stable urinary metabolites of thromboxane A2 and prostacyclin, 11-dehydro-thromboxane B2 (11-dehydro-TXB2) and 2,3-dinor-6-keto-prostaglandin F1alpha (2,3-dinor-6-keto-PGF1alpha) were measured in diabetics to elucidate the relation between the thromboxane A2/prostacyclin (TX/PGI) balance and pathological states of diabetes mellitus. 11-Dehydro-TXB2 and 2,3-dinor-6-keto-PGF1alpha were derivatized to methyl ester-propylamide-dimethylisopropylsilyl ether and methyl ester-methoxime-dimethylisopropylsilyl ether derivatives, respectively, and applied to a gas chromatography/selected ion monitoring. The TX/PGI ratios of diabetics were higher than those of healthy volunteers, suggesting the hypercoagulative states of this disease. The ratios showed positive correlations with the levels of blood glucose. The levels of hemoglobin A1c and triglyceride were correlated weakly with the ratio. Some of the patients who had relatively low levels of blood glucose also showed high TX/PGI ratios. Furthermore, the ratio increased in the order of the groups 1, 2, and 3; group 1 contained patients who did not take medicine for diabetes, group 2 contained those who took oral hypoglycemic agents, and group 3 contained those who received insulin therapy. These observations indicate that the TX/PGI ratio reflects the pathological conditions of diabetes and is a useful marker, having few different features from other markers that are presently used.

Reduced prostacyclin to thromboxane A2 ratio is correlated with central apneas in preterm infants.

Prostacyclin has a vasodilating effect on pulmonary vessels, whereas thromboxane A2 results in vasoconstriction. This study was designed to test the hypothesis that recurrent central apneas in preterm infants are correlated with a reduced prostacyclin to thromboxane A2 ratio. Twelve preterm infants with clinical events of apneas were matched with 12 control infants. Urinary concentration of 2,3-dinor-6-keto-PGF1alpha and 2,3-dinor-TxB2 was determined, and the ratio correlated with the number of central apneas (>20s) measured in overnight polygraphy. The number of central apneas >20s/12h was 97.4 (SE 7.8) in the study group, and 47.3 (SE 6.6) in the control group (p = 0.001). There was a significant correlation between the number of central apneas and the 2,3-dinor-6-keto-PGF1alpha/2,3-dinor-TxB2-ratio in all infants combined (r = -0.72, p < 0.0001) as well as in the two subject groups. Central apneas in premature infants are correlated with an decreased prostacyclin to thromboxane A2 ratio. The underlying pathomechanism may be increased intrapulmonary shunts with reflexive central apneas due to reduced pulmonary oxygenation.

Allergen-induced synthesis of F(2)-isoprostanes in atopic asthmatics. Evidence for oxidant stress.

It is thought that reactive oxygen species (ROS) participate in the inflammation which characterizes asthma, but the evidence supporting this contention is incomplete. F(2)-isoprostanes (F(2)-IsoPs) are arachidonate products formed on membrane phospholipids by the action of ROS and thereby represent a quantitative measure of oxidant stress in vivo. Using a mass spectrometric assay we measured urinary release of F(2)-IsoPs in 11 patients with mild atopic asthma after inhaled allergen challenge. The excretion of F(2)-IsoPs increased at 2 h after allergen (1.5 +/- 0.2 versus 2.6 +/- 0.3 ng/mg creatinine) and remained significantly elevated in all urine collections for the 8-h period of the study (analysis of variance [ANOVA]). The measured compounds were of noncyclooxygenase origin because neither aspirin nor indomethacin given before challenge suppressed them. Urinary F(2)-IsoPs remained unchanged after inhaled methacholine challenge. In nine atopic asthmatics, F(2)-IsoPs were quantified in bronchoalveolar lavage fluid (BALF) at baseline values and in a separate segment 24 h after allergen instillation. F(2)-IsoPs were elevated late in the BALF (0.9 +/- 0.2 versus 11.4 +/- 3.0 pg /ml, baseline versus allergen, respectively, p = 0.007). The increase was inhibited by pretreatment of the subjects with inhaled corticosteroids. These findings provide a new evidence for a role for ROS and lipid peroxidation in allergen-induced airway inflammation.

Leukotriene (LT)-receptor antagonist is more effective in asthmatic patients with a low baseline ratio of urinary LTE4 to 2,3-dinor-6-keto-prostaglandin (PG)F1alpha.

BACKGROUND: To test the hypothesis that urinary levels of arachidonic acid metabolites may be a predicting factor of the effects of pranlukast, a selective leukotriene (LT) antagonist, on chronic adult asthma, we investigated the relationship between its clinical efficacy and urinary eicosanoid levels. METHODS: An open, multicenter trial was conducted involving 38 stable moderate and severe asthmatic patients (mean percent predicted FEV1 was 71%). All patients received pranlukast (225 mg twice daily) for 4 weeks after a 2-week run-in period. Urinary levels of LTE4, 11-dehydro-thromboxane (TX) B2, 2,3-dinor-6-keto-prostaglandin (PG) F1alpha, and creatinine were measured in 3-h urine collected on day 1 of the treatment. The responder was defined by an improvement of asthma symptom scores and peak expiratory flow rate (PEFR). RESULTS: One patient was excluded because of an adverse effect, nausea. Thirteen out of 37 subjects were responders and 24 were nonresponders. There were no significant differences in patients' backgrounds and urinary arachidonate levels between the two groups. The urinary LTE4 to 2,3-dinor-6-keto-PGF1alpha ratio in the responder was significantly lower (P=0.01) than that in the nonresponder. In all patients, a significant inverse correlation was revealed between the baseline urinary LTE4/2,3-dinor-6-keto-PGF1alpha ratio and the improvement of PEFR in the morning (r=-0.43, P=0.007). CONCLUSIONS: These data suggested that the urinary ratio of LTE4 to 2,3-dinor-6-keto-PGF1alpha might be one of the predictive markers of the clinical efficacy of this LT-receptor antagonist in asthmatic subjects.

Prostanoid formation during feeding of a preterm formula with long-chain polyunsaturated fatty acids in healthy preterm infants during the first weeks of life.

The objective of this study was to evaluate the effect of conventional and long-chain polyunsaturated fatty acids (LCP)-enriched preterm formula on prostanoid formation in preterm infants during their first weeks of life. In a prospective, randomized, double-blind study, healthy infants received either formula enriched with LCP (n = 10), standard preterm formula (n = 10), or (expressed) breast milk (n = 10). Urine was sampled, and anthropometric measurements were taken at study entry and after the study period of 3 wk. In vivo formation of prostaglandin E2, thromboxane A2, and prostacyclin was evaluated by measuring the urinary excretion of the respective index metabolities by gas chromatography-mass spectrometry. There were no significant differences in urinary prostanoid excretion and anthropometric data between the groups at the end of the study period. We conclude that neither conventional formula nor supplementation of a preterm formula with LCP for a period of 3 wk substantially influence prostanoid formation in healthy preterm infants.

Effects of imidazole-salicylate on renal function and the diuretic action of furosemide in cirrhotic patients with ascites.

Imidazole-salicylate is a non-steroidal anti-inflammatory drug with limited inhibitory effects on prostaglandin synthesis. The renal effects of this drug were investigated by a double-blind cross-over study in 10 patients with cirrhosis and ascites. Two therapeutic doses of imidazole-salicylate (750 mg each) were given at midnight and 08:00 h and 80 mg of furosemide were injected intravenously at 09:00 h. The same procedure was followed on another day but a placebo replaced imidazole-salicylate. Renal function (creatinine clearance, free water and electrolyte excretions) and urinary excretion of prostaglandin E, 6-keto-prostaglandin F1 alpha and thromboxane B2 were evaluated for 8 h after the first dose of the drug and for 2 h after furosemide injection. Platelet thromboxane production was also determined 9 h after the first administration of drug or placebo. Imidazole-salicylate did not affect renal function or inhibit kidney prostanoid production either under basal conditions or after the stimulating effect of furosemide. On the contrary, imidazole-salicylate significantly inhibited platelet thromboxane production (45.8 +/- 9 vs. 69.4 +/- 7.5 ng/ml, P < 0.05). These results suggest that imidazole-salicylate is an anti-inflammatory drug that can be given to patients with decompensated cirrhosis without risk of inhibiting kidney prostaglandin synthesis or the renal response to furosemide.

Extracorporeal shock wave lithotripsy induces the release of prostaglandins which increase ureteric peristalsis.

The aim of this study was to identify the changes in secretion of prostaglandins into the urinary tract as a result of treatment by extracorporeal shock wave lithotripsy (ESWL) and to determine their effects on ureteric motility. Sixteen patients with renal or upper ureteric calculi were studied. A peripheral blood and urine sample was collected immediately before and after ESWL, with further samples taken 24 h later. The following variables were assessed by radioimmunoassay:prostaglandin E2 (PGE2), prostaglandin F1 alpha (PGF1 alpha), and thromboxane B2 (TXB2). An in vitro canine study was then designed to study the activity of TXB2, PGF1 alpha and PGE2 on an isolated intact canine ureter model. Significant elevations of TXB2 were found immediately after ESWL in both serum and urine, which fell almost to pre-treatment levels by 24 h. PGF1 alpha levels showed significant elevations at 24 h but no immediate increase as seen with TXB2. In contrast, PGE2 levels were unchanged in the urine but significantly decreased in the serum. In vitro studies showed that both TXB2 and PGF1 alpha repeatedly produced an increased frequency of ureteric contraction. ESWL results in the release of prostaglandins from the urinary tract which are shown to cause increased ureteric peristalsis.