6-ketoprostaglandin-f1-alpha and Chronic-Disease

Mechanisms responsible for anti-ischemic benefits of enhanced external counterpulsation (EECP) remain unknown. This was the first randomized sham-controlled study to investigate the extracardiac effects of EECP on peripheral artery flow-mediated dilation.. Forty-two symptomatic patients with coronary artery disease were randomized (2:1 ratio) to thirty-five 1-hour sessions of either EECP (n=28) or sham EECP (n=14). Flow-mediated dilation of the brachial and femoral arteries was performed with the use of ultrasound. Plasma levels of nitrate and nitrite, 6-keto-prostaglandin F(1α), endothelin-1, asymmetrical dimethylarginine, tumor necrosis factor-α, monocyte chemoattractant protein-1, soluble vascular cell adhesion molecule, high-sensitivity C-reactive protein, and 8-isoprostane were measured. EECP increased brachial (+51% versus +2%) and femoral (+30% versus +3%) artery flow-mediated dilation, the nitric oxide turnover/production markers nitrate and nitrite (+36% versus +2%), and 6-keto-prostaglandin F(1α) (+71% versus +1%), whereas it decreased endothelin-1 (-25% versus +5%) and the nitric oxide synthase inhibitor asymmetrical dimethylarginine (-28% versus +0.2%) in treatment versus sham groups, respectively (all P<0.05). EECP decreased the proinflammatory cytokines tumor necrosis factor-α (-16% versus +12%), monocyte chemoattractant protein-1 (-13% versus +0.2%), soluble vascular cell adhesion molecule-1 (-6% versus +1%), high-sensitivity C-reactive protein (-32% versus +5%), and the lipid peroxidation marker 8-isoprostane (-21% versus +1.3%) in treatment versus sham groups, respectively (all P<0.05). EECP reduced angina classification (-62% versus 0%; P<0.001) in treatment versus sham groups, respectively.. Our findings provide novel mechanistic evidence that EECP has a beneficial effect on peripheral artery flow-mediated dilation and endothelial-derived vasoactive agents in patients with symptomatic coronary artery disease.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Angina Pectoris; Blood Pressure; Brachial Artery; C-Reactive Protein; Chronic Disease; Counterpulsation; Cytokines; Endothelin-1; Exercise Tolerance; Femoral Artery; Humans; Middle Aged; Nitric Oxide; Oxygen Consumption; Regional Blood Flow; Tumor Necrosis Factor-alpha; Vasodilation

To investigate the effects of bepridil on silent myocardial ischemia and on eicosanoid metabolism, 10 patients with chronic stable angina underwent exercise treadmill testing and 48-hour ambulatory electrocardiographic monitoring both before and after 4 weeks of bepridil administration (150 mg/day). Fasting venous levels of thromboxane B2, 6-keto-prostaglandin F1 alpha, and leukotriene C4 were measured by radioimmunoassay. Bepridil decreased heart rate responses to daily activities during ambulatory monitoring, and significantly (p < 0.05) reduced the median frequency and duration of silent myocardial ischemic episodes (from 5.5 to 0 events/48 hours and from 86 to 0 minutes/48 hours respectively). Bepridil significantly decreased the blood pressure heart rate product at peak exercise and significantly prolonged the mean exercise tolerance time (from 456.6 to 527.0 second). Bepridil also significantly decreased the plasma levels of thromboxane B2 and leukotriene C4 at rest. These results suggest that bepridil may reduce silent myocardial ischemic episodes either by the reduction of cardiac oxygen demand during daily activities and exercise stress, or by controlling coronary and systemic vasomotor tone. The drug also has a salutary effect on eicosanoid metabolism, to which its efficacy on silent myocardial ischemic episodes may be related.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Angina Pectoris; Arachidonic Acids; Bepridil; Chronic Disease; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Rate; Humans; Leukotriene C4; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Radioimmunoassay; Single-Blind Method; Thromboxane B2

The purpose of the current investigation was to study the influence of sulindac and naproxen on renal function and urinary excretion of the stable hydration product of prostacyclin, 6-keto-PGF1 alpha, in patients with arthritis and impaired renal function.. In a placebo-controlled, double-blind, cross-over design, the effects of 7 days of oral sulindac 200 mg twice a day were compared with naproxen 500 mg in the morning and 250 mg in the evening in 10 patients with polyarthritis and stable impaired renal function. Inulin and para-amino-hippurate sodium were used to calculate glomerular filtration rate and renal plasma flow. The excretion rate of 6-keto-PGF1 alpha was measured in urine collected overnight. After patients ingested drugs in the morning, urine was collected in fractions by spontaneous voiding. Venous blood samples were drawn repeatedly for assay of electrolytes, creatinine, proteins, hormones, and drugs. Grip strength and Ritchie articular index were recorded as indicators of symptomatic antiarthritic effectiveness.. Naproxen decreased urine levels of 6-keto PGF1 alpha by 59% (p less than 0.01). Sulindac had no effect on renal prostaglandin excretion. Naproxen reduced the glomerular filtration rate and renal plasma flow by 18% (p less than 0.05) and 13% (p less than 0.05), respectively, while no significant change was observed during the sulindac treatment periods. Serum levels of creatinine and complement factor D were unaffected by either drug. Plasma renin activity decreased during naproxen and sulindac treatments by 38% (p less than 0.05) and 22% (p less than 0.05). No significant change in plasma aldosterone was observed during the two drug treatments, but urinary aldosterone declined significantly (p less than 0.05) by 34% with naproxen. Albuminuria decreased (p less than 0.05) during both naproxen (41%) and sulindac treatment (72%), while the albumin/creatinine clearance ratio decreased by 59% (p less than 0.05) only during treatment with sulindac. N-acetyl-beta-D-glucosaminidase in urine was not changed by either drug. Sulindac and naproxen had no discernible effects on base excess, excretion of water, sodium, or potassium, or on osmolal clearance. However, serum potassium increased slightly but significantly (p less than 0.01) during treatment with naproxen. Sulindac sulfide, the active metabolite of sulindac, could not be traced in the urine from any of the patients. Mean arterial blood pressure declined significantly (p less than 0.05) during sulindac treatment but did not change during treatment with naproxen. Both drugs produced equal clinical improvement as measured by grip strength and the Ritchie articular index.. The results suggest that when sulindac and naproxen are given in clinical equipotent doses to patients with impaired renal function, sulindac does not affect renal prostaglandin synthesis or renal function, whereas naproxen induces suppression of renal prostaglandin synthesis and a further decrease in renal function.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Arthritis, Rheumatoid; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Naproxen; Placebos; Potassium; Renal Circulation; Renin; Sodium; Sulindac

We investigated whether the glomerular synthesis of prostacyclin modulates the renal blood flow and glomerular filtration rate in chronic glomerular disease. The urinary excretion of 6-keto-prostaglandin F1 alpha, a stable breakdown product of prostacyclin, was significantly (P less than 0.01) reduced in 20 women with chronic glomerular disease, as compared with 19 controls, whereas excretion of urinary prostaglandin E2 was unchanged. In 10 patients randomly assigned to one week of treatment with ibuprofen, excretion of urinary 6-keto-prostaglandin F1 alpha and prostaglandin E2 was reduced by 80 per cent, the level of serum creatinine was increased by 40 per cent, and creatinine and para-aminohippurate clearances were reduced by 28 and 35 per cent, respectively. The reduction of both clearances was inversely related (P less than 0.01) to the basal urinary excretion of 6-keto-prostaglandin F1 alpha but not of prostaglandin E2. No functional changes were detected in five healthy women, despite a similar suppression of renal prostacyclin synthesis by ibuprofen. In contrast, one week of treatment with sulindac did not affect renal prostacyclin synthesis or renal function in the other 10 patients, despite a marked inhibition of extrarenal cyclooxygenase activity. We conclude that in patients with mild impairment of renal function, the renal blood flow and glomerular filtration rate are critically dependent on prostacyclin production. In such patients sulindac may be a safe substitute for other nonsteroidal antiinflammatory drugs.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Chronic Disease; Creatinine; Dinoprostone; Epoprostenol; Female; Glomerular Filtration Rate; Glomerulonephritis; Humans; Ibuprofen; Indenes; Kidney; Kidney Glomerulus; Middle Aged; p-Aminohippuric Acid; Prostaglandins E; Renal Circulation; Sulindac

To explore the changes of the neurotransmitters in patients with chronic pulmonary heart disease (CPHD) and its clinical significance.. Seventy-two patients with CPHD (42 males, 30 females, mean age 55.6-/+8.9 years) were enrolled in the study, including 48 patients with compensated CPHD and 24 with uncompensated CPHD. Plasma endothelin (ET), thromboxance B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-K-PGFlalpha) were detected by radioimmunoassay. Thirty blood donors were selected as the normal control.. Compared with the normal controls, CPHD patients showed abnormal pulmonary function, and significantly elevated levels of plasma ET and TXB2 (P<0.01) and lowered 6-K-PGFlalpha(P<0.01), but no significant differences were found between the patients with compensated CPHD and uncompensated CPHD (P>0.05). Plasma ET and TXB2 levels were inversely correlated to 6-K-PGFlalpha level (r=-0.4571, P<0.05).. The patients with CPHD present with obvious changes of plasma ET, TXB2 and 6-K-PGFlalpha.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Case-Control Studies; Chronic Disease; Endothelins; Female; Humans; Male; Middle Aged; Pulmonary Heart Disease; Thromboxane B2

To assess the synergistic action of famotidine (FMD) and chlorpheniramine (CPA) on acetic acid-induced chronic gastric ulcer in rats.. Chronic gastric lesions were induced in male Sprague-Dawley (SD) rats by serosal application of the acetic acid. Forty SD rats were randomly divided into blank group (n = 8), control group (n = 8), FMD group (n = 8), CPA group (n = 8), and FMD+CPA group (n = 8). Each group was given intraperitoneally (i.p.) 0.5 mL/100 g distilled water, 9 g/L NaCl saline, 4 mg/kg FMD, 10 mg/kg CPA, 4 mg/kg FMD+10 mg/kg CPA, respectively, daily for 10 d. On d 10, ulcer area was determined by planimetry. The level of myeloperoxidase (MPO) in the liver homogenization was determined by biochemical methods and the plasma levels of 6-ketoprostaglandin F1 alpha (6-keto-PGF(1a)) and IL-8 were determined by radioimmunoassay.. The synergistic effects of FMD+CPA group on the lesion, IL-8, 6-keto-PGF(1a) and MPO were confirmed. The effect of FMD+CPA group was significantly different as compared to the control and FMD groups. The lesion (mm(2)) was reduced from 40.18+/-2.6 in control group to 6.83+/-2.97 in PMD+CPA group, P<0.01, and from 32.9+/-3.27 in FMD group to 6.83+/-2.97 in PMD+CPA group, P<0.01. The plasma levels of IL-8 decreased from 0.69+/-0.11 ng/L in control group to 0.4+/-0.04 ng/L in PMD+CPA group, P<0.01, and from 0.51+/-0.08 ng/L in FMD group to 0.4+/-0.04 ng/L in PMD+CPA group, P<0.05. The level of 6-keto-PGF(1a) increased from 7.55+/-1.65 ng/L in control group to 16.62+/-0.97 ng/L in PMD+CPA group, P<0.01, and from 13.15+/-1.48 ng/L in FMD group to 16.62+/-0.97 ng/L in PMD+CPA group, P<0.05. The levels of MPO in the liver homogenate decreased from 9.12+/-2.05 u/L in control group to 4.33+/-0.95 u/L in PMD+CPA group, P<0.01, and from 8.3+/-1.29 u/L in FMD group to 4.33+/-0.95 u/L, P<0.01.. The synergistic action of FMD and CPA on acetic acid-induced chronic gastric ulcer in rats decreases the incidence of ulcer and also enhances the healing of ulcer.

Topics: 6-Ketoprostaglandin F1 alpha; Acetic Acid; Animals; Chlorpheniramine; Chronic Disease; Drug Synergism; Famotidine; Histamine H1 Antagonists; Histamine H2 Antagonists; Interleukin-8; Liver; Male; Peroxidase; Rats; Rats, Sprague-Dawley; Stomach Ulcer

Our purpose was to determine whether production of arachidonic acid metabolites, particularly cyclooxygenase (COX) metabolites, is altered in 100-400-microm-diameter pulmonary arteries of piglets at an early stage of pulmonary hypertension. Piglets were raised in either room air (control) or hypoxia for 3 days. A cannulated artery technique was used to measure responses of 100-400-microm-diameter pulmonary arteries to arachidonic acid, a prostacyclin analog, or the thromboxane mimetic. Radioimmunoassay was used to determine pulmonary artery production of thromboxane B(2) (TxB(2)) and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), the stable metabolites of thromboxane and prostacyclin, respectively. Assessment of abundances of COX pathway enzymes in pulmonary arteries was determined by immunoblot technique. Arachidonic acid induced less dilation in pulmonary arteries from hypoxic than in pulmonary arteries from control piglets. Pulmonary artery responses to prostacyclin and were similar for both groups. 6-Keto-PGF(1alpha) production was reduced, whereas TxB(2) production was increased in pulmonary arteries from hypoxic piglets. Abundances of both COX-1 and prostacyclin synthase were reduced, whereas abundances of both COX-2 and thromboxane synthase were unaltered in pulmonary arteries from hypoxic piglets. At least partly due to altered abundances of COX pathway enzymes, a shift in production of arachidonic acid metabolites, away from dilators toward constrictors, may contribute to the early phase of chronic hypoxia-induced pulmonary hypertension in newborn piglets.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; 6-Ketoprostaglandin F1 alpha; Animals; Animals, Newborn; Arachidonic Acid; Chronic Disease; Cyclooxygenase 1; Cyclooxygenase 2; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Hypertension, Pulmonary; Hypoxia; Intramolecular Oxidoreductases; Isoenzymes; Prostaglandin-Endoperoxide Synthases; Pulmonary Artery; Reference Values; Swine; Thromboxane B2; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

To investigate the clinical effect and therapeutic mechanism of Nanmiqing capsule made of rheum palmatum, leech, astragalus memberanaceus on patients with chronic prostatitis(CP).. Seventy-six CP cases were treated with Nanmiqing, while 32 CP cases were treated with Qianliekang as a control. The changes of EPS were observed pre- and post-treatment. The rat model of CP got by Xiaozhiling inducing were treated with Nanmiqing and Qianliekang respectively. The concentration of endothelin, TXB2, 6-keto-PGF1 alpha and SOD, IgG, IgA in plasma were measured pre- and post-treatment, meanwhile, pathological changes of prostate tissues were observed.. The total effective rate was 89.47% in treatment group, which was significantly higher than 71.88% in the control group (P < 0.01). Experimental study for CP rats showed that the Nanmiqing was more effective medicine than Qianliekang (P < 0.01).. Nanmiqing was an effective medicine for CP. The mechanism of clearing heat and resolving toxin, activating blood and removing stasis and reinforcing Qi in chinese medicine could be the explanation of the useful treatment including three therapentic ways.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Capsules; Chronic Disease; Drugs, Chinese Herbal; Endothelin-1; Humans; Immunoglobulin A; Immunoglobulin G; Male; Middle Aged; Prostatitis; Superoxide Dismutase; Thromboxane B2; Treatment Outcome

The regulation of pulmonary prostacyclin synthesis is not completely understood. We tested the hypothesis that prostacyclin production is predominantly stimulated by hemodynamic factors, such as increased shear-stress, and is thus increased in rats with chronic hypoxic pulmonary hypertension.. To this end, we determined pulmonary prostacyclin synthase (PGIS) gene expression, circulating levels of the stable prostacyclin metabolite 6-keto prostaglandin F(1alpha) (6-keto-PGF(1alpha)), pulmonary endothelin (ET)-1 gene expression, and ET-1 plasma levels in rats exposed to 4 weeks of hypoxia (10% O(2)) in the presence or absence of either the nitric oxide (NO) donor molsidomine (MD, 15 mg/kg/day) or the ET-A receptor antagonist LU135252 (LU, 50 mg/kg/day).. Right ventricular systolic pressure (RVSP), the cross-sectional medial vascular wall area of pulmonary arteries, and ET-1 production increased significantly during hypoxia. PGIS mRNA levels increased 1.7-fold, and 6-keto-PGF(1alpha) plasma levels rose from 8.2+/-0.8 to 12.2+/-2.2 ng/ml during hypoxia (each P<0.05 vs. normoxic controls). MD and LU reduced RVSP and pulmonary vascular remodeling similarly (each P<0.05 vs. hypoxia), but only MD inhibited pulmonary ET-1 formation (P<0.05 vs. hypoxia). Nevertheless, both drugs attenuated the increase in PGIS gene expression and plasma 6-keto-PGF(1alpha) levels (each P<0.05 vs. hypoxia).. Our data suggest that prostacyclin production in hypertensive rat lungs is predominantly increased by hemodynamic factors while hypoxia, NO and ET-1 per are less important stimuli, and that this increase may serve as a compensatory mechanism to partially negate the hypoxia-induced elevation in pulmonary vascular tone.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Chronic Disease; Cytochrome P-450 Enzyme System; Endothelin Receptor Antagonists; Endothelin-1; Hypertension, Pulmonary; Hypoxia; Intramolecular Oxidoreductases; Male; Models, Animal; Molsidomine; Nitric Oxide Donors; Phenylpropionates; Pulmonary Artery; Pyrimidines; Random Allocation; Rats; Rats, Wistar; Receptor, Endothelin A; RNA, Messenger; Systole; Ventricular Pressure

The aim of this study was to investigate the role of arachidonic acid metabolites (AAMs) in the pathogenesis of antrochoanal polyp (ACP). Using high-performance liquid chromatography (HPLC), we assayed the tissue concentrations of 6-keto-PGF1alpha, leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETE). Concentrations of AAMs in ACP were compared with the level in the control turbinate tissues and nasal polyps associated with chronic paranasal sinusitis (NPS). The concentrations of 6-keto-PGF1alpha were not significantly different in the control turbinate, ACP and NPS groups. In ACP, concentrations of LTC4, 15-HETE and 12-HETE were significantly lower than in the control turbinate. The striking differences in the profile of AAMs between ACP and NPS included a lack of production of LTD4 and LTE4 in ACP, also detectable in NPS, and markedly lower concentrations of 15-HETE and 12-HETE in ACP. The results of this study indicate that decreased lipoxygenase pathway products in arachidonic acid metabolism may be involved in the pathogenesis of ACP. However, in the pathogenesis of NPS, increased production of LTD4 and LTE4 may have an important role. Taken together, our results demonstrate a difference in pathogenesis between ACP and NPS, particularly in terms of arachidonic acid metabolism.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Arachidonic Acid; Child; Chromatography, High Pressure Liquid; Chronic Disease; Humans; Hydroxyeicosatetraenoic Acids; Leukotrienes; Nasal Polyps; Sinusitis; Turbinates

The aim of this study was to assess prospectively the urinary excretion of renal and systemic metabolites of thromboxane and prostacyclin in normotensive and chronic hypertensive pregnancies.. Pregnant hospital employees were invited to collect 24-hour urine samples weekly from the seventh week until delivery. Concentrations of renal metabolites (thromboxane B2, 6-keto-prostaglandin F1alpha) were measured by radioimmunoassay after extraction. Systemic metabolites (2,3-dinor-thromboxane B2, 2,3-dinor-6-keto-prostaglandin F1alpha) were assessed by enzyme immunoassay after extraction and high-pressure liquid chromatographic separation.. Thromboxane B2 excretion was similar in normotensive and hypertensive pregnancies, whereas a twofold increase of 6-keto-prostaglandin F1alpha was observed in hypertensive compared with normotensive pregnancies (7537 +/- 349 vs 3857 +/- 202 pg/mg creatinine, p < 0.001). During pregnancy in both conditions measurements displayed uniform excretion of thromboxane B2 with progressively increased levels of 6-keto-prostaglandin F1alpha in chronic hypertension (R2 = 0.60, p < 0.005). Mean excretion of 2,3-dinor-thromboxane B2 averaged 1208 +/- 65 and 898 +/- 48 pg/mg creatinine in normotensive and hypertensive pregnancies (p < 0.001), mainly due to significant decreased concentrations in hypertension in the first half of pregnancy. Conversely, 2,3-dinor-6-keto-prostaglandin F1alpha levels were 845 +/- 39 and 1226 +/- 67 pg/mg creatinine in normotensive and hypertensive pregnancies (p < 0.001), mostly because of significantly increased production in hypertension from 22 weeks onward. Ratios of both renal and systemic metabolites favored increased prostacyclin production in chronic hypertension.. In contrast to preeclampsia, uncomplicated mild to moderate chronic hypertensive pregnancies are characterized by an excess production of prostacyclin with unaltered or even lower thromboxane concentrations, which may contribute to the general favorable outcome of this hypertensive condition.

Topics: 6-Ketoprostaglandin F1 alpha; Chronic Disease; Creatinine; Epoprostenol; Female; Humans; Hypertension; Kidney; Longitudinal Studies; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Prospective Studies; Reference Values; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Child; Child, Preschool; Chronic Disease; Dinoprost; Dinoprostone; Female; Humans; Hydronephrosis; Male; Prostaglandins; Pyelonephritis; Reference Values; Renin; Sodium; Thromboxane B2; Vesico-Ureteral Reflux

A comparative study of prevalence of periodontal diseases in an indigenous Armenian population and a population of refugees in Armenia has been performed. The refugees population was considered a population of subjects under permanent stress conditions. It has been shown that in the refugees population there are higher prevalence of periodontal diseases, first of all periodontitis, and more marked heaviness of injures in periodontal tissues that those in the indigenous population. These changes were accompanied with elevated signs of disturbances of hemo-endothelial balance. In particular, there were profound alterations of normal ratio of 6-keto-PGF1a/NXB2 and increased level of markers for endothelial disorganization, thrombomodulin and von Willebrand factor, in the blood. It is that stress-induced disturbances of the hemo-endothelial balance among the refugees may contribute to developing periodontal diseases in this population.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Armenia; Chronic Disease; Female; Humans; Male; Middle Aged; Periodontal Diseases; Periodontal Index; Prevalence; Random Allocation; Refugees; Stress, Psychological; Thrombomodulin; Thromboxanes; von Willebrand Factor

Nineteen patients with symptoms of chronic venous insufficiency (CVI) were treated with 13-week cycles of intermittent pneumatic compression (IPC) during 2 h sessions twice weekly, with most treatments at home. At study completion, quantitative subjective scores for total symptomatology were improved in 16/19 patients (84%). Enhancement of fibrinolytic potential in vivo was detected in 86% of observations on specimens from CVI patients over 2 h of IPC, with accelerated euglobulin clot lysis times (ELT) noted within 15 min of initiating compression. The enhanced fibrinolytic potential was attributed to increased urokinase plasminogen activator (u-PA), probably released from perturbed endothelial cells by IPC. Significant decreases in total t-PA antigen (mass concentration) but not t-PA activity, were produced by IPC in CVI patients only (P = 0.0001), with greater effects noted in the non-anticoagulated versus the anticoagulated cohort. Plasminogen activator inhibitor type 1 (PAI-1) levels rose rapidly after IPC only in the controls and non-anticoagulated CVI patients. PAI-1 decreased in those receiving anticoagulation. No platelet perturbation was detected during IPC by measuring levels of beta-thromboglobulin or the thromboxane A2 metabolite, 11-dehydrothromboxane B2; however, significant (P < 0.003) decreases in plasma prostacyclin (PGI2) levels (measured as the stable 6-ketoprostaglandin F-1-alpha-metabolite) were observed after 15 min of IPC in non-anticoagulated CVI patients only. There was no evidence of increased thrombin generation by IPC, determined by urinary excretion of fibrinopeptide A and prothrombin fragment 1. Concurrent anticoagulation appears to mediate more favorable biochemical alterations in CVI, although subjective improvement did not correlate with anticoagulation. The mechanism(s) by which these physiologic changes compliment the mechanical effects of IPC remain to be elucidated and will require adequately controlled and powered studies.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; beta-Thromboglobulin; Chronic Disease; Female; Fibrinolysis; Humans; Male; Middle Aged; Platelet Activation; Pressure; Thrombophlebitis; Tissue Plasminogen Activator; Venous Insufficiency

Prostacyclin (PGI2) and thromboxane A2 (TXA2) play an important role in the pathophysiology of various cardiovascular diseases. The balance between PGI2 and TXA2 regulates the interaction between platelets and the vessel wall in vivo. In this study we measured PGI2 and TXA2 synthesis by analysing their urinary index metabolites 2,3-dinor-6-keto-PGF1 alpha and 11-dehydro-TXB2, respectively, in acute (10 patients) and chronic (10 patients) lower limb ischaemia. Both PGI2 and TXA2 synthesis were increased about two-fold in patients with acute lower limb ischaemia compared to chronic lower limb ischaemia. However, the PGI2/TXA2 ratio was more or less the same in acute and chronic lower limb ischaemia. In patients with acute lower limb ischaemia caused by thrombotic occlusion, PGI2 and TXA2 formation were about two times higher than in patients with acute lower limb ischaemia caused by embolic occlusion. Elevation of PGI2 and TXA2 synthesis in acute lower limb ischaemia may reflect increased platelet-vascular wall interactions without changing the PGI2/TXA2 ratio.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aged, 80 and over; Chronic Disease; Creatinine; Epoprostenol; Extremities; Female; Humans; Ischemia; Male; Middle Aged; Thrombosis; Thromboxane A2; Thromboxane B2

In the present study, the role of endogenous prostanoid synthesis in gastric mucosa in the healing of chronic gastric ulcers was investigated. Nineteen patients were divided into two groups in accordance with healing state after one month of treatment with cimetidine only: "healed group" and "unhealed group". Biopsy specimens taken from the mucosa around the ulceration (damaged gastric mucosa) and at a distance from the ulceration (normal gastric mucosa) at endoscopy prior to treatment were homogenized, and the mucosal prostanoid synthesis was determined using [14C]arachidonic acid. The mean value of prostaglandin E2 synthesis in the normal gastric mucosa of the healed group was 60% higher than in that of the unhealed group, but the difference was not significant. However, prostaglandin E2 synthesis in the damaged gastric mucosa of the healed group was 117% higher than in that of the unhealed group. The same tendency was observed for prostaglandin D2 and 6-keto prostaglandin F1 alpha synthesis as for prostaglandin E2. In our study it was demonstrated that there is a good correlation of prostaglandin synthesis in the damaged mucosa with healing of chronic gastric ulceration. Furthermore, our study indicated that prostaglandin synthesis, especially in damaged mucosa, might be important in the healing of gastric ulceration.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Autoradiography; Chronic Disease; Cimetidine; Dinoprostone; Female; Gastric Mucosa; Humans; Male; Middle Aged; Prostaglandin D2; Prostaglandins; Stomach Ulcer

Pancreatic production of lipid mediators of inflammation, including eicosanoids and platelet-activating factor (PAF), was examined in two models of pancreatitis in the rat. Chronic pancreatitis was induced by ligation of the pancreatic duct and acute pancreatitis by infusion of sodium taurocholate into the pancreatic duct. In the model of chronic pancreatitis, prostaglandin E2 (PGE2), PGD2, 6-keto PGF1 alpha, thromboxane B2 (TXB2), and PAF increased significantly in the pancreas in a similar fashion, whereas leukotriene B4 (LTB4) remained unchanged. BN52021, a PAF antagonist, reduced the accumulation of pancreatic TXB2, 6-keto PGF1 alpha, and PGD2, and did not affect PGE2. In the model of acute pancreatitis, LTB4 increased, whereas PGE2, TXB2, and 6-keto PGF1 alpha decreased significantly; PGD2 changed slightly; and PAF was undetectable. The present results indicate that mild chronic pancreatitis is accompanied by the production and accumulation of a wide spectrum of lipid mediators while LTB4 was the only lipid mediator detected at biologically active concentrations in the model of severe acute pancreatitis. It is suggested that various mediators are involved in establishing a balance between inflammation and the repair of the inflamed pancreatic tissue observed in mild chronic pancreatitis. While both eicosanoids and PAF are involved in such self-limiting responses to inflammatory challenge, PAF seems to play a central role in instigating the production of the various other mediators detected in the model of chronic pancreatitis. In the model of acute pancreatitis while the deficiency of various lipid mediators may render the pancreatic tissue more susceptible to acute damage, enhanced LTB4 appears to contribute to the destructive pathology observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Chronic Disease; Dinoprostone; Diterpenes; Eicosanoids; Ginkgolides; Lactones; Leukotriene B4; Ligation; Male; Masoprocol; Pancreatic Ducts; Pancreatitis; Platelet Activating Factor; Prostaglandin D2; Rats; Rats, Sprague-Dawley; Taurocholic Acid; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Chronic Disease; Female; Gastric Juice; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Peptic Ulcer; Prostaglandins; Thromboxane B2

Specific features of the prostacyclin-thromboxan system were revealed in 122 newborns with perinatal hypoxia of various severity in the course of the early neonatal period. Differences in blood prostacyclin and thromboxan levels and their ratio were revealed in newborns who suffered different forms of hypoxia and adaptation disturbances of varying severity. The most pronounced and stubborn changes were characteristic of infants with a history of grave chronic intrauterine hypoxia.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adaptation, Physiological; beta-Thromboglobulin; Chronic Disease; Epoprostenol; Fetal Hypoxia; Humans; Infant, Newborn; Thromboxane B2

The authors investigated in 19 patients with chronic proliferative glomerulonephritis the effect of 100 mg acetylsalicylic acid (ACA) administered for 12 months and the effect of 50 mg ACA administered for the same period. They evaluated the effect of the two doses on the urinary excretion of PGI and TXA2 metabolites as well as the effect on proteinuria and glomerular filtraction (GF). The authors provided evidence that small and very small amounts of ACA did not affect the excretion of the PGI metabolite, while they reduced significantly the excretion of the TXA2 metabolite and of proteinuria, and significantly increased GF.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aspirin; Chronic Disease; Creatinine; Female; Glomerular Filtration Rate; Glomerulonephritis; Humans; Male; Middle Aged; Proteinuria; Thromboxanes

Gingival crevicular fluid, collected from 8 patients with chronic adult periodontitis before and 21 days after root planing and scaling, was analysed for prostaglandin E2, 6KPGF1 alpha, cAMP, IgG, IgM and alpha-2-macroglobulin, and their inter-relationship evaluated. There was a significant decrease in the levels of prostaglandin E2, IgG, IgM and alpha-2-macroglobulin after treatment, whereas the levels of 6KPGF1 alpha and cAMP remained essentially unchanged. The level of prostaglandin E2 decreased by 35%, IgG by 32%, IgM by 90%, and alpha-2-macroglobulin by 79%. There was a significant degree of correlation between prostaglandin E2 and 6KPGF1 alpha and cAMP before treatment but not after, but no correlation between prostaglandin E2 and IgG, IgM and alpha-2-macroglobulin either before or after. This correlation pattern indicates the involvement of E2, prostaglandin 6KPGF1 alpha and cAMP in inflammation in the periodontium. The changes in IgG, IgM and alpha-2-macroglobulin reflect yet another mechanism of host response which appears to be independent of prostaglandins.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; alpha-Macroglobulins; Chronic Disease; Cyclic AMP; Dental Scaling; Dinoprostone; Gingival Crevicular Fluid; Humans; Immunoglobulin G; Immunoglobulin M; Periodontitis; Tooth Root

A study was made of the content of leukotriene B4, prostacycline and thromboxane A2 in the fluid of bronchoalveolar lavage in 62 patients with chronic bronchitis (CB) in the stage of exacerbation and remission. The time course of changes in the concentration of the eukosanoids was compared with the status of pulmonary local defense factors and cellular immunity. In catarrhal obstructive bronchitis, an important mechanism of a steady maintenance of bronchial obstruction involved a rise of the content of leukotriene B4 whereas in purulent obstructive bronchitis, it was an excess level of thromboxane A2. It is assumed that immunologically dependent activation of the leukotriene B4 and thromboxane synthetase capacity of alveolar macrophages may stipulate the clinical course of CB, modulating the bronchoconstrictor or inflammatory component of the disease. To correct phlogogenous function of alveolar macrophages, the use of immunomodulating therapy with a selective action on the suppressor component of immunity is desirable.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Bronchitis; Bronchoalveolar Lavage Fluid; Bronchoscopy; Chronic Disease; Epoprostenol; Humans; Immunity, Cellular; Leukotriene B4; Middle Aged; Thromboxane A2; Thromboxane B2

This paper reports on investigations of the formation of PGI2 and TXA2 using their stabile products 6-keto-PGF1 alpha and TXB2 (RIA) in liver biopsy specimens of 46 patients suffering from fatty liver (n = 19), chronic hepatitis B (n = 11), liver cirrhosis (n = 13), and miscellaneous diseases (n = 3). The measured formation rates in chronic liver disease were evaluated in comparison to a reference group (n = 19) consisting of minimal liver lesions. The 6-keto-PGF1 alpha formation correlating to the degree of the portal inflammation in the liver (morphometric evaluation). The same trend existed in relation to the intralobular inflammation. The results presented suggest in respect of analogous data in animal experiments that PGI2 is predominantly generated in mesenchymal cells of the liver and, presumably influences the course of liver diseases.

Topics: 6-Ketoprostaglandin F1 alpha; Chronic Disease; Epoprostenol; Female; Humans; Liver; Liver Diseases; Male; Thromboxane A2; Thromboxane B2

Noradrenaline levels in the superior cervical ganglion and sciatic nerve were significantly reduced in chronic streptozotocin-induced diabetes in rats. Sciatic nerve sheath in vitro biosynthesis of 6-keto prostaglandin F1 alpha (6KPGF1 alpha; the stable metabolite of prostacyclin) was significantly reduced but not in acute experimental diabetes. Nerves with reduced 6KPGF1 alpha had an excessive response to arachidonic acid stimulation. We suggest that the reduced endogenous biosynthesis of prostacyclin is due to reduced substrate availability, possibly due to the reduced noradrenaline. The implications of these findings on the pathogenesis of diabetic neuropathy are discussed. Neuropathy was found to involve all fibre populations studied (motor, sensory and sympathetic) and progressed with duration of diabetes.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Chronic Disease; Diabetes Mellitus, Experimental; Electrophysiology; Ganglia, Sympathetic; Male; Norepinephrine; Rats; Rats, Inbred Strains; Sciatic Nerve; Streptozocin

The role of leukotrienes in the pathogenesis of chronic colitis was investigated using a rat model. Ulceration and inflammation of the distal colon was initiated by the intracolonic administration of the hapten trinitrobenzene sulfonic acid in 50% ethanol. Leukotriene B4 synthesis increased significantly within 4 h after induction of damage, with the greatest increase observed 24-72 h after administration of the hapten. The increase in leukotriene B4 synthesis correlated well (r = 0.88) with an increase in colonic myeloperoxidase activity, a biochemical marker of neutrophil infiltration. Daily intracolonic treatment with a specific 5-lipoxygenase inhibitor, L651,392, during the first 4 days after initiation of colitis, resulted in significant reductions of colonic leukotriene B4 synthesis, colonic damage score, and colon wet weight. When examined 2 wk after initiation of colitis, the group treated with L651,392 (for the first 4 days) showed significantly less colonic damage (assessed macroscopically and histologically) and colonic inflammation (assessed histologically and by measurement of myeloperoxidase activity). The healing produced by treatment with L651,392 was comparable to that observed after treatment with 5-aminosalicylic acid in a similar manner. Although a reduction of colonic damage could be produced in this model by intracolonic pretreatment with a prostaglandin E1 analogue (rioprostil), the mechanism of action of L651,392 did not appear to be through prevention of the initial injury induced by the hapten and ethanol solution. These results demonstrate that inhibition of leukotriene synthesis results in a marked acceleration of the healing of colonic ulcers and resolution of colonic inflammation in this animal model of chronic colitis. The results are therefore consistent with the hypothesis that leukotrienes play an important role in the pathogenesis of intestinal inflammation.

Topics: 6-Ketoprostaglandin F1 alpha; Aminosalicylic Acids; Animals; Chronic Disease; Colitis; Colon; Leukotriene B4; Lipoxygenase Inhibitors; Male; Mesalamine; Peroxidase; Phenothiazines; Prostaglandins E; Rats; Rats, Inbred Strains; Rioprostil

Products of the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism were estimated in the cul-de-sac fluid from patients with endometriosis, pelvic adhesions and normal laparoscopic examinations, with and without chronic pelvic pain. No correlation between the symptoms, underlying diagnoses, and the concentrations of eicosanoids were observed.

Topics: 6-Ketoprostaglandin F1 alpha; Abdominal Pain; Arachidonic Acid; Arachidonic Acids; Ascitic Fluid; Chronic Disease; Dinoprostone; Eicosanoids; Endometriosis; Female; Genital Diseases, Female; Humans; Laparoscopy; Leukotriene B4; Pelvis; Tissue Adhesions

In 14 patients with chronic proliferative glomerulonephritis, corrected arterial hypertension and normal or marginal glomerular filtration the authors assessed plasmatic and urinary metabolites of PGI2 and TXA2. They found that the production of both PGI2 and TXA2 was raised in the organism and they assume that in the stimulated synthesis hypertension and its treatment participated. The production of both prostaglandins in the kidneys was, however, normal.

Topics: 6-Ketoprostaglandin F1 alpha; Chronic Disease; Epoprostenol; Female; Glomerulonephritis, Membranoproliferative; Humans; Male; Prostaglandins; Thromboxane A2; Thromboxane B2

In adult diabetic subjects and infants of diabetic mothers, hyperglycemia has been associated with increased intravascular thromboxane and decreased prostacyclin production. Because of the association between states of altered insulin concentration and prostaglandin metabolism, we hypothesized that chronic experimentally induced fetal hyperinsulinemia results in perturbations in fetal arachidonic acid and prostaglandin metabolism. Arachidonic acid, thromboxane B2 (the stable breakdown product of thromboxane A2), and 6-keto-prostaglandin F1 alpha (the stable breakdown product of prostacyclin) were determined in the arterial blood of chronically catheterized fetal sheep after 9 to 12 days of continuous insulin (15 U.day-1, n = 7) or placebo (n = 5) infusion. Fetal insulin infusion resulted in fetal hypoglycemia and a reduction in fetal arterial plasma arachidonic acid concentration (p less than 0.01). In addition, the concentration of thromboxane B2 relative to 6-keto-prostaglandin F1 alpha was significantly reduced in the insulin-treated group compared with the placebo-treated group (p less than 0.03). We conclude that fetal hyperinsulinemia in sheep produces perturbations in prostaglandin metabolism with reductions in the plasma arachidonic acid concentration and in the plasma concentration of thromboxane A2 relative to prostacyclin. The hyperinsulinemic-hypoglycemic state in the fetus influences the relative proportion of the vasoconstricting to the vasodilating prostaglandins, thereby potentially modulating fetal vasomotor tone.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acids; Chronic Disease; Female; Fetal Diseases; Hyperinsulinism; Insulin; Pregnancy; Prostaglandins; Sheep; Thromboxane B2

The blood plasma levels of a number of endogenous prostaglandins have been measured by column chromatography followed by radioimmunoassay in 33 patients with psoriasis and in 22 children with allergic dermatoses. The findings evidence an increase of these prostanoids at the peak of the skin process exacerbation, thus indicating their role in the pathogenesis of psoriasis and allergic dermatoses in children.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Child; Child, Preschool; Chronic Disease; Dermatitis, Atopic; Humans; Infant; Middle Aged; Neurodermatitis; Psoriasis; Thromboxane B2

Bone resorption is a common finding in chronic otitis media with or without cholesteatoma. The etiology of bone resorption in chronic otitis media is still not clear. Bone-resorbing activity of prostaglandins (PGs) has been well known. PGE-like material has been detected in granulation tissue. However, there have been no reports on the comprehensive study of PGs in cholesteatomas or granulation tissue. The purpose of this study is to show that PGs are synthesized in the middle ear tissue and to report concentrations of PGs in cholesteatomas and granulation tissue. Samples of cholesteatoma and granulation tissues were obtained at the time of tympanomastoidectomies. Prostaglandin synthesizing activity was determined by incubating tissue with labeled arachidonic acid (precursor of PGs) and radiochromatography. Levels of PGs were determined by radioimmunoassay. Arachidonic acid metabolites produced in cholesteatoma and granulation tissue included PGE2; 6-keto-PGF1 alpha; PGF2 alpha; PGD2; and 5-, 12-, and 15-hydroxy-eicosatetraenoic acid (HETE). Levels of PGE2 were 2.6 times higher in cholesteatoma (106.8 +/- 46 ng/g) than in granulation tissue (41.0 +/- 14.3 ng/g). Levels of 6-keto-PGF1 alpha were two times higher in granulation tissue (89.0 +/- 27.0 ng/g) than in cholesteatoma. Levels of thromboxane B2 were two times higher in cholesteatoma than in granulation tissue. The results of this study demonstrate that cholesteatoma and granulation tissues actively synthesize PGs and contain high concentrations of them. Since PGs are locally active hormones, the presence of PGs indicates an active role for PGs in the pathogenesis of chronic otitis media with bone resorption.

Topics: 6-Ketoprostaglandin F1 alpha; Bone Resorption; Cholesteatoma; Chronic Disease; Dinoprost; Dinoprostone; Granulation Tissue; Humans; Hydroxyeicosatetraenoic Acids; Otitis Media; Prostaglandins; Thromboxane B2

Two different methods of causing myocardial oxygen demand and supply imbalance; symptom limited treadmill exercise and right atrial pacing stimulation, were used to examine the alteration of hemodynamics and the effects upon sympathetic nerve activities, platelet functions and prostaglandin synthesis in patients with coronary artery disease (CAD). Age and sex distributions, the cardiothoracic ratio, left ventricular end-diastolic pressure, ejection fraction and coronary artery obstructions of the patients did not differ significantly between the two tests. Arterial blood samples were obtained to assay for plasma catecholamine, beta-thromboglobulin (beta TG), platelet factor 4 (PF4), TXB2 (thromboxane B2) and 6 keto-PGF1-alpha (6 ketoprostaglandin F1-alpha) without any difficulties before and immediately after testing. The arterial systolic pressure and pressure rate product (PRP) were changed more significantly by treadmill exercise than pacing, while the DPTI/TTI (diastolic pressure time index/tension time index) ratio and ST segment deviations showed similar changes with both tests. The plasma NE (norepinephrine) level, beta TG, PF4, and TXB2/6 keto-PGF1-alpha were significantly elevated by treadmill exercise, but not by pacing. 6 keto-PGF1-alpha was not markedly affected by either tests. There were no significant differences between the patients with and without anginal pain either in hemodynamics or metabolites. Significant relationships were observed between changes in plasma NE levels and the PRP (r = 0.76, n = 26, p less than 0.01) and also changes in the arterial systolic pressure (r = 0.64, n = 26, p less than 0.01), but there were no significant correlations between any other hemodynamic parameters with plasma NE, platelet function, prostaglandin activity, or between each metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; beta-Thromboglobulin; Cardiac Pacing, Artificial; Chronic Disease; Coronary Disease; Electrocardiography; Epinephrine; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Platelet Factor 4; Thromboxane B2

Blood endogenous prostaglandins, E, F2 alpha, prostacyclin and thromboxane levels were measured in the ascending aorta and the coronary sinus of 32 patients (29 males and 3 females) with paroxysmal supraventricular arrhythmias (atrial fibrillation and supraventricular tachycardia) during the sinus rhythm and an arrhythmic paroxysm. Group 1 was made up by 22 patients with idiopathic cardiac rhythm disorders, and group 2 comprised 10 coronary patients with arrhythmias. A relationship was demonstrated between cardiac endogenous prostanoids balance and the clinical pattern of cardiac rhythm abnormality (duration and frequency of paroxysms) as well as changes in cardiac prostanoid rations associated with tachyarrhythmic paroxysms.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Chronic Disease; Coronary Disease; Dinoprost; Female; Humans; Male; Middle Aged; Prostaglandins; Prostaglandins E; Prostaglandins F; Tachycardia, Paroxysmal; Tachycardia, Supraventricular; Thromboxane B2

Peritoneal fluid obtained at laparoscopy from 49 women was measured for its content of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), 6-keto-prostaglandin F1 alpha (6-KF), and thromboxane B2 (TxB2) by specific radioimmunoassays. In normal women (n = 10), the concentrations of prostaglandins in peritoneal fluid were (mean +/- SE): PGE2 = 0.79 +/- 0.26, PGF2 alpha = 0.60 +/- 0.18, 6-KF = 0.48 +/- 0.19, and TxB2 = 0.23 +/- 0.09 ng/ml; in women with endometriosis (n = 16): PGE2 = 1.43 +/- 0.72, PGF2 alpha = 1.52 +/- 0.59, 6-KF = 3.32 +/- 0.71, and TxB2 = 1.14 +/- 0.69 ng/ml; in women with chronic pelvic inflammatory disease and/or obstructed tubes (n = 19): PGE2 = 1.94 +/- 1.04, PGF2 alpha = 1.20 +/- 0.61, 6-KF = 1.55 +/- 0.40, and TxB2 = 0.64 +/- 0.24 ng/ml; in women with pelvic pain without any visible pathologic condition (n = 4): PGE2 = 1.11 +/- 0.66, PGF2 alpha = 0.73 +/- 0.55, 6-KF = 1.35 +/- 0.35, and TxB2 = 0.39 +/- 0.17. The mean volumes of peritoneal fluid recovered were 10 to 16 ml and were not significantly different between the groups. Except for a significantly elevated concentration of 6-KF in the peritoneal fluid of women with endometriosis compared to normal women (p = less than 0.02), the prostaglandins measured did not differ significantly between the groups of women studied. The possible significance of elevated 6-KF in the peritoneal fluid of women with endometriosis is discussed.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Ascitic Fluid; Chronic Disease; Dinoprost; Dinoprostone; Endometriosis; Epoprostenol; Female; Humans; Pain; Pelvic Inflammatory Disease; Pelvis; Prostaglandins; Prostaglandins E; Prostaglandins F; Thromboxane A2

To explore the possible vasoregulatory role of renal prostaglandins during liver disease, excretory rates of PGE2, PGF2 alpha, and a metabolite of PGI2, 6k-PGF1 alpha, were determined before and after chronic ligation of the common bile duct in 23 dogs. Bile duct ligation for 50 +/- 3.7 days (mean +/- SEM) significantly increased serum bilirubin and alkaline phosphatase. PGE2, PGF2 alpha, and 6k-PGF1 alpha excretion rates were significantly (p less than 0.01) increased following chronic bile duct ligation, by approximately 100%, 80%, and 500%, respectively, with similar increments in both ascitic and nonascitic animals. In 10 sham-ligated animals, PGE2, PGF2 alpha, and 6k-PGF1 alpha excretion rates were unchanged. In 6 dogs sequential measurements of urine prostaglandins indicated that PGE2 and 6k-PGF1 alpha excretion were significantly increased at 2, 4, and 6 weeks after ligation, whereas the increase in PGF2 alpha excretion was not significant until 6 weeks. Indomethacin (2 mg/kg) reduced prostaglandin excretion by 65% to 90% and significantly increased arterial pressure, decreased glomerular filtration rate and renal blood flow, and increased renal vascular resistance from 0.53 +/- 0.09 to 0.90 +/- 0.13 mm Hg/ml/min. Fractional renal blood flow, assessed by microspheres, was disproportionately reduced in the inner cortex after prostaglandin inhibition in the chronic bile duct ligation group. Indomethacin did not significantly alter renal function in sham animals, despite comparable reductions in prostaglandin excretion. These data demonstrate that, in dogs with experimental liver disease produced by chronic bile duct ligation, renal prostaglandin synthesis is increased, and the enhanced synthesis of vasodilatory prostaglandins serves to maintain renal blood flow and glomerular filtration rate.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Chronic Disease; Common Bile Duct; Dogs; Female; Kidney; Ligation; Liver Diseases; Prostaglandins; Prostaglandins E; Prostaglandins F

Prostacyclin production in neonates born at various gestational ages (28 weeks to term) was compared with that in neonates born of pregnancies complicated by various acute and chronic placental insufficiency states. Prostacyclin levels were reflected by the amount of conversion of 14C arachidonic acid to 6-keto-PGF1 alpha (the stable end-product of prostacyclin) by umbilical arteries. The uptake of 14C arachidonic acid by the umbilical arteries was also determined, and since this was similar for all groups it was not the cause of the differences noted in prostacyclin production. Neonates born of normal pregnancies had similar levels of prostacyclin production regardless of gestational age. Prostacyclin production was very low in neonates born of pregnancies complicated by chronic placental insufficiency (intrauterine growth retardation, essential hypertension, and pre-eclampsia), but normal with acute placental insufficiency (abruptio placentae). Hence the decrease in fetal prostacyclin production in pre-eclampsia is not related to gestational age; furthermore, it is also seen in other chronic placental insufficiency states.

Topics: 6-Ketoprostaglandin F1 alpha; Abruptio Placentae; Chronic Disease; Epoprostenol; Female; Gestational Age; Humans; Hypertension; Placenta Diseases; Placental Insufficiency; Pregnancy; Pregnancy Complications, Cardiovascular; Prostaglandins; Prostaglandins F; Syndrome; Umbilical Arteries

The activation of platelets due to foreign surface interaction is a well known fact. Earlier, we found an increase of circulating platelet microaggregates (method of Wu and Hoak) during hemodialysis. Since this phenomenon might cause a PGI2-release by lung and/or vascular tissue, we studied the plasma 6-oxo-PGF 1 alpha-levels in 6 patients during hemodialysis. We found an initial increase of plasma 6-oxo-PGF 1 alpha. Coincidently, hypoxemia, fall in platelet and lekocyte count and a decrease in platelet count ratio were observed. An effect of heparin was excluded in a control group. The findings support the hypothesis that PGI2 acts as a defense mechanism against platelet deposition on vascular wall by a temporary increased synthesis which could be monitored by a temporarily enhanced plasma 6-oxo-PGF 1 alpha-level during the initial phase of hemodialysis.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Chronic Disease; Female; Humans; Leukocyte Count; Male; Middle Aged; Oxygen; Platelet Aggregation; Platelet Count; Prostaglandins F; Renal Dialysis; Uremia

In acute and chronic kidney transplant rejection renal cortical and medullary tissue samples were examined for their prostacyclin (PGI2) generation by bioassay and compared with normal tissue. In acute rejection PGI2 formation was significantly enhanced, particularly in the cortex. In chronic rejection the PGI2 formation was comparable with control tissue. Since PGI2 is a very potent platelet aggregation inhibitor and vasodilator, it is concluded that the increase in PGI2 generation in acute rejection might be a self protecting mechanism which is, however, overwhelmed in irreversible rejection.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Chronic Disease; Epoprostenol; Graft Rejection; Humans; Kidney Cortex; Kidney Medulla; Kidney Transplantation; Prostaglandins; Prostaglandins F; Transplantation, Homologous