thromboxane-b2 and Chronic-Disease

Marine-derived n-3 polyunsaturated fatty acids (PUFA) may have a beneficial effect on inflammation via lowering pro-inflammatory eicosanoid concentrations. We aimed to assess the effect of marine-derived n-3 PUFA on prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and leukotriene B4 (LTB4) through systematic review and meta-analysis of randomized controlled trials.. A structured search strategy on PubMed, Web of Science and Cochrane up to November 2015 was undertaken in this meta-analysis. Standard mean difference was used to calculate the effect size of marine-derived n-3 PUFA on PGE2, TXB2 and LTB4 in a random-effect model. A total of 18 RCTs with 826 subjects were included in this systematic review and meta-analysis. Supplementation of marine-derived n-3 PUFA significantly decreased concentrations of TXB2 in serum/plasma in subjects with high risk of cardiovascular diseases (SMD:-1.26; 95% CI: -1.65, -0.86) and LTB4 in neutrophils in unhealthy subjects (subjects with non-autoimmune chronic diseases or auto-immune diseases) (SMD:-0.59: 95% CI: -1.02, -0.16). Subgroup analyses showed a significant reduction of LTB4 in subjects with rheumatoid arthritis (SMD: -0.83; 95% CI: -1.37, -0.29), but not in non-autoimmune chronic disease patients (SMD: -0.33; 95% CI: -0.97, 0.31). No significant publication bias was shown in the meta-analysis.. Marine-derived n-3 PUFA had a beneficial effect on reducing the concentration of TXB2 in blood of subjects with high risk of CVD as well as LTB4 in neutrophils in unhealthy subjects, and that subjects with RA showed lower LTB4 content with supplementation of marine-derived n-3 PUFA.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Chronic Disease; Dietary Supplements; Dinoprostone; Dose-Response Relationship, Drug; Eicosanoids; Fatty Acids, Omega-3; Fish Oils; Humans; Leukotriene B4; Randomized Controlled Trials as Topic; Research Design; Thromboxane B2; Treatment Outcome

In contrast to a variety of clinical conditions characterized by ineffective circulatory volume, chronic glomerular disease is not usually associated with increased circulating levels of vasoconstrictor hormones. However, a reduction in glomerular prostacyclin production can possibly account for the prostaglandin dependence of renal function in these patients by virtue of the enhanced constrictor effects of angiotensin II on glomerular arterioles and mesangium. The reduction of renal function induced by a nonselective cyclo-oxygenase inhibitor is inversely related to the basal prostacyclin production. Increased renal synthesis of vasoconstrictor thromboxane A2, as noted in patients with systemic lupus erythematosus, might contribute to the cyclo-oxygenase dependence of renal function. Aspirin as well as a variety of structurally unrelated nonsteroidal anti-inflammatory drugs reduce renal function in systemic lupus erythematosus patients. However, the functional consequences of renal cyclo-oxygenase inhibition are partially attenuated in patients with lupus nephritis vis-à-vis other forms of chronic glomerular disease because of concomitant suppression of enhanced glomerular thromboxane A2 production. Animal data consistent with a prevailing functional significance of vasodilator prostaglandins have also been reported. Short-term administration of sulindac at the recommended dosage is relatively safe in patients with chronic glomerular disease because of selective sparing of glomerular cyclo-oxygenase activity. The long-term consequences of selective versus nonselective cyclo-oxygenase inhibition remain to be established in humans. The beneficial effects of a combination of aspirin and dipyridamole in slowing the deterioration of renal function in patients with membranoproliferative glomerulonephritis does provide a rationale for exploring the effects of low-dose aspirin (i.e., 0.5 to 1.0 mg/kg per day), which most effectively suppresses platelet thromboxane A2 production without interfering with renal prostacyclin synthesis.

Topics: Animals; Anti-Inflammatory Agents; Blood Platelets; Chronic Disease; Cyclooxygenase Inhibitors; Humans; Kidney; Kidney Diseases; Kidney Glomerulus; Prostaglandins; Thromboxane B2

It has been reported that the biosynthesis of thromboxane A2 (TXA2) is enhanced in platelets in the presence of chronic obstructive pulmonary disease (COPD), and 11-dehydro-TXB2, a urinary metabolite of thromboxane, also increases in blood. In the present study, seratrodast (CAS 112665-43-7, Bronica), a TXA2 receptor antagonist, was administered to 14 patients with chronic pulmonary emphysema in the stable phase for 8 weeks. Respiratory distress was evaluated in the attending physicians' judgments using the Hugh-Jones (H-J) classification, and also by the patients themselves using the Borg scale. Respiratory function tests, including forced vital capacity (FVC), percent of one second forced expiratory volume (FEV1.0%), arterial blood gases during respiration of room air, and peak expiratory flows (PEF) (morning and evening), and measurement of plasma 11-denhydro-TXB2 and TXB2 levels were performed before and 8 weeks after the start of administration, as well as at the time of the start of administration. The results revealed significant improvement of respiratory distress, evaluated on both the H-J classification and the Borg scale, at week 8. Although no significant changes were observed in plasma TXB2 levels, the plasma 11-dehydro-TXB2 level significantly decreased at week 8. Among the respiratory function parameters examined, only FVC was significantly improved. These results indicated that seratrodast is useful for the improvement of respiratory distress in patients with chronic pulmonary emphysema in the stable phase.

Topics: Aged; Aged, 80 and over; Anti-Asthmatic Agents; Benzoquinones; Carbon Dioxide; Chronic Disease; Dyspnea; Female; Forced Expiratory Volume; Heptanoic Acids; Humans; Immunoglobulin E; Male; Middle Aged; Oxygen; Peak Expiratory Flow Rate; Prostaglandin Antagonists; Pulmonary Emphysema; Respiratory Function Tests; Smoking; Thromboxane A2; Thromboxane B2

It has been suggested that daily intake of aspirin is associated with a reduction of cognitive decline, both in normal and in demented subjects, but the mechanism is unclear. We have therefore studied the relationship between thromboxane (TX) A(2) biosynthesis, as reflected by the urinary excretion of 11-dehydro-TXB(2), and the presence of dementia in patients after acute stroke.. Patients from the Rotterdam Stroke Databank were screened for dementia between 3 and 9 months after stroke. Patients had a full neurological examination, neuropsychological screening, and, if indicated, extensive neuropsychological examination. Criteria used for the diagnosis of dementia were from the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (Revised). Urine samples were taken at the time of screening. Urinary 11-dehydro-TXB(2) was measured by means of a previously validated radioimmunoassay.. Dementia was diagnosed in 71 patients, and urine samples were available for 62. Median value (range) of 11-dehydro-TXB(2) was 399 (89 to 2105) pmol/mmol creatinine for demented patients versus 273 (80 to 1957) for 69 controls with stroke but without dementia (P=0.013). No difference was found between 44 patients with vascular dementia, 404 (89 to 2105) pmol/mmol creatinine, and 18 patients with Alzheimer's disease plus cerebrovascular disease, 399 (96 to 1467) pmol/mmol creatinine (P=0.68). In a stepwise logistic regression analysis, in which possible confounders such as use of antiplatelet medication, cardiovascular risk factors, and type of stroke were taken into account, increased urinary excretion of 11-dehydro-TXB(2) remained independently related to the presence of dementia (OR 1.12, 95% CI 1.03 to 1.22 per 100 pmol/mmol creatinine). The difference in metabolite excretion rates between demented and nondemented patients was most prominent within the subgroup of ischemic stroke patients who received aspirin (P<0.01).. Increased thromboxane biosynthesis in the chronic phase after stroke is associated with the presence of but not the type of poststroke dementia. It is particularly apparent in patients on aspirin, thereby suggesting the involvement of extraplatelet sources of TXA(2) production in this setting.

Topics: Aged; Aspirin; Biomarkers; Blood Platelets; Brain Ischemia; Cerebral Hemorrhage; Chronic Disease; Cognition; Creatinine; Dementia, Vascular; Female; Humans; Male; Platelet Aggregation Inhibitors; Prognosis; Prospective Studies; Radioimmunoassay; Thromboxane A2; Thromboxane B2

One of the causes of coronary artery spasm in patients with variant angina could be a disturbed interaction between the vasodilating action of endothelial derived relaxing factor and the vasospastic action of neuropeptide Y and thromboxane B2. The aim of this study was a verification of the participation of neuropeptide Y and thromboxane B2 in etiopathogenesis of the coronary artery spasm in patients with variant angina. The survey was made in 38 patients with variant angina and in 18 patients with chronic stable angina pectoris. The control group consisted of 20 healthy persons. Before the hyperventilation test, during which the person under test has been breathing with a frequency of 40/minute through 5 minutes, the Tris (tromethamol) of pH = 10.5 has been given in intravenous infusion lasting for 5 minutes. The neuropeptide Y and thromboxane B2 plasma levels have been determined just before the hyperventilation test, just after the termination of the test and 10 minutes after the termination of the test. Neuropeptide Y and thromboxane B2 plasma levels have been determined with a radioimmunologic method. It has been recorded that during the hyperventilation test in all of the 38 patients with variant angina the clinical and the electrocardiographic symptoms of the coronary artery spasm have appeared--but these have not appeared in patients with chronic stable angina pectoris and in healthy persons. The level of neuropeptide Y in patients with variant angina before the test, just at its end and as well as 10 min. after completing of the hyperventilation test, was significantly higher compared with the level in patients with chronic stable angina pectoris and controls. Contrary to chronic stable angina pectoris patients and controls, in variant angina group the level of neuropeptide Y increased rapidly at the end of the test and further elevation in neuropeptide Y level was observed 10 min. after the test. There was no difference in basal thromboxane B2 levels between angina patients and controls. At the end of hyperventilation test in variant angina group thromboxane B2 level significantly increased and remained on this level until 10 min. after the test. Significant increase of neuropeptide Y and thromboxane B2 plasma levels in variant angina patients during artery coronary spasm induced by hyperventilation test suggests the contribution of these humoral factors to the pathogenesis of vasospastic episodes in angina patients.

Topics: Adult; Angina Pectoris; Angina Pectoris, Variant; Chronic Disease; Female; Humans; Male; Middle Aged; Neuropeptide Y; Thromboxane B2

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

Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) has been shown to reduce proteinuria in experimental models of renal diseases, but their potential role in the treatment of human renal disease is unknown. We administered n-3 PUFA in the form of triglycerides [with eicosapentaenoic (EPA)+docosahexaenoic (DHA) = 3 g/day into 4 patients] and of ethyl esters (EPA+DHA = 7.7 g/day) into 10 patients (one patient twice) with chronic glomerular disease (membranous glomerulonephritis and focal glomerular sclerosis), all diagnosed histologically. Serum albumin was > 2.4 g/dl and serum creatinine < 2.5 mg/dl in all patients. Treatment was given for periods of six weeks, followed by a prolonged follow-up for 27 weeks in 10 cases. Dietary supplementation with n-3 PUFA caused the expected reduction in platelet generation of thromboxane B2 (mean +/- SEM, from 490 +/- 70 ng/ml at baseline, to 342 +/- 147 ng/ml at 6 weeks, P < 0.05) of serum triglycerides (from 236 +/- 60 to 170 +/- 43, P < 0.01), and a prolongation of the bleeding time (from 5.8 +/- 0.4 min to 7.7 +/- 0.4 min, P < 0.01) in patients treated with ethyl esters. A modest but significant reduction in serum total cholesterol was noticed (from 275 +/- 27 to 252 +/- 24 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aged, 80 and over; Blood Pressure; Cholesterol; Chronic Disease; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; Male; Middle Aged; Proteinuria; Thromboxane B2

Platelet activation is involved in acute coronary syndromes (ACS). Incomplete suppression by low-dose aspirin treatment of thromboxane (TX) metabolite excretion (urinary 11-dehydro-TXB2) is predictive of vascular events in high-risk patients. Myeloid-related protein (MRP)-8/14 is a heterodimer secreted on activation of platelets, monocytes, and neutrophils, regulating inflammation and predicting cardiovascular events. Among platelet transcripts, MRP-14 has emerged as a powerful predictor of ACS.. We enrolled 68 stable ischemic heart disease (IHD) and 63 ACS patients, undergoing coronary angiography, to evaluate whether MRP-8/14 release in the circulation is related to TX-dependent platelet activation in ACS and IHD patients and to residual TX biosynthesis in low-dose aspirin-treated ACS patients. In ACS patients, plasma MRP-8/14 and urinary 11-dehydro-TXB2 levels were linearly correlated (r=0.651, P<0.001) but significantly higher than those in IHD patients (P=0.012, P=0.044) only among subjects not receiving aspirin. In aspirin-treated ACS patients, MRP-8/14 and 11-dehydro-TXB2 were lower versus those not receiving aspirin (P<0.001) and still significantly correlated (r=0.528, P<0.001). Higher 11-dehydro-TXB2 significantly predicted higher MRP-8/14 in both all ACS patients and ACS receiving aspirin (P<0.001, adj R(2)=0.463 and adj R(2)=0.497) after multivariable adjustment. Conversely, plasma MRP-8/14 (P<0.001) and higher urinary 8-iso-prostaglandin F2α (P=0.050) levels were significant predictors of residual, on-aspirin, TX biosynthesis in ACS (adjusted R(2)=0.384).. Circulating MRP-8/14 is associated with TX-dependent platelet activation in ACS, even during low-dose aspirin treatment, suggesting a contribution of residual TX to MRP-8/14 shedding, which may further amplify platelet activation. Circulating MRP-8/14 may be a target to test different antiplatelet strategies in ACS.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Calgranulin A; Calgranulin B; Chronic Disease; Dinoprost; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Platelet Activation; Platelet Aggregation Inhibitors; Thromboxane B2

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

In a previous study, we reported a new gamma-hydroxybutenolide derivative, 4-benzo[b]thiophen-2-yl-3-bromo-5-hydroxy-5H-furan-2-one (BTH), as inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1) expression in lypopolysaccharide (LPS) stimulated RAW 264.7 and TPH-1 cells, without affecting cyclooxygenase-2 (COX-2). In this study, we evaluated the in vivo effect of BTH on some acute and chronic inflammatory animal models in relation to its inhibitory profile on mPGES-1 expression. In the zymosan-induced mouse air pouch model, BTH produced a dose-dependent inhibition of prostaglandin E(2) (PGE(2)) production and mPGES-1 protein expression in pouch exudates without any effect on COX-2 protein expression. This behavior was confirmed in the chronic model of collagen-induced arthritis, where administration of BTH (5 mg/kg) clearly reduced PGE(2) and mPGES-1 expression in joint tissues, whereas COX-2 was unaffected. These effects were accompanied by the suppression of clinical and histopathological manifestations of disease such as the loss of proteoglycan, and the destruction of surface cartilage. Other enzymes participating in the metabolism of arachidonic acid, such as prostaglandin I(2) synthase, tromboxane A(2) synthase or 5-lipoxygenase were unaffected by this compound. The acetic acid-induced hyperalgesia model in LPS-sensitized mice showed a dose-dependent analgesic effect of BTH, exerting an ED(50) value of 6.2 mg/kg. Our data suggest that inhibition of mPGES-1 protein expression in acute and chronic inflammatory models by BTH, could provide a potential therapeutic target and a pharmacological tool to discern the role of the inducible enzymes COX-2 and mPGES-1 in inflammatory pathologies.

Topics: 4-Butyrolactone; Acetates; Analgesics; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Behavior, Animal; Blood Platelets; Cattle; Chronic Disease; Gene Expression Regulation, Enzymologic; Humans; Hyperalgesia; Inflammation; Intramolecular Oxidoreductases; Leukotriene B4; Male; Mice; Neutrophils; Prostaglandin-E Synthases; Thiophenes; Thromboxane B2

Trypanosoma cruzi induces inflammatory reactions in several tissues. The production of prostaglandin F2alpha, 6-keto-prostaglandin F1alpha and thromboxane B2, known to regulate the immune response and to participate in inflammatory reactions, was studied in mice experimentally infected with T. cruzi. The generation of nitric oxide (NO), which could be regulated by cyclooxygenase metabolites, was also evaluated. In the acute infection the extension of inflammatory infiltrates in skeletal muscle as well as the circulating levels of cyclooxygenase metabolites and NO were higher in resistant C3H mice than in susceptible BALB/c mice. In addition, the spontaneous release of NO by spleen cells increased earlier in the C3H mouse strain. In the chronic infections, the tissue inflammatory reaction was still prominent in both groups of mice, but a moderate increase of thromboxane B2 concentration and in NO released by spleen cells was observed only in C3H mice. This comparative study shows that these mediators could be mainly related to protective mechanisms in the acute phase, but seem not to be involved in its maintenance in the chronic T. cruzi infections.

Topics: Acute Disease; Animals; Chagas Disease; Chronic Disease; Dinoprostone; Disease Susceptibility; Epoprostenol; Inflammation; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Muscle, Skeletal; Nitric Oxide; Prostaglandin-Endoperoxide Synthases; Species Specificity; Spleen; Thromboxane A2; Thromboxane B2

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

By inhibiting prostaglandin synthesis, aspirin can interfere with both arterial functional and angiotensin-converting enzyme inhibitor (ACEI) properties and be deleterious in chronic heart failure (CHF).. Our aim was to prospectively evaluate the effect of aspirin on arterial functional properties in CHF patients treated with ACEIs.. Over three consecutive treatment periods of 7 days, 18 patients received placebo, followed by aspirin 100 mg/day, and then aspirin 325 mg/day. Single blind prospective assessment of reflected wave and time reflection by radial applanation tonometry; pulse wave velocity; blood pressure; thromboxane B2 (TxB2) and prostaglandins in plasma and urine was performed. Aspirin 325 mg/day induced a significant increase in augmentation index of reflected wave (P<0.0001 and P=0.0013 vs. placebo and aspirin 100 mg, respectively) and a significant decrease in reflected wave traveling times (P=0.0007 vs. placebo). Aspirin 100 mg/day produced a similar, though non-significant, trend in these parameters compared with placebo. Both aspirin treatments produced a statistically significant decrease in serum TxB2 (P<0.0001) but did not have an effect on the metabolite of prostaglandin I2 (P=0.136).. This study demonstrates the existence of a dose-mediated deleterious effect of aspirin upon arterial functional properties in CHF patients treated with ACEI.

Topics: Adult; Aged; Aged, 80 and over; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Arteries; Aspirin; Blood Pressure; Chronic Disease; Controlled Clinical Trials as Topic; Cyclooxygenase Inhibitors; Diastole; Dose-Response Relationship, Drug; Enalapril; Endpoint Determination; Female; Heart Failure; Heart Rate; Humans; Lisinopril; Male; Manometry; Middle Aged; Observer Variation; Prospective Studies; Ramipril; Renin; Reproducibility of Results; Single-Blind Method; Systole; Thromboxane B2; Time Factors; Treatment Outcome

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

We investigated the effects of FR122047 (1-[(4,5-bis(4-methoxyphenyl)-2-thiazoyl)carbonyl]-4-methylpiperazine hydrochloride), a selective cyclo-oxygenase (COX)-1 inhibitor, in rat type II collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA). Using an ex vivo rat whole blood assay, FR122047 (0.032 - 3.2 mg kg(-1)) inhibited COX-1-derived thromboxane (TX) B(2) production with ED(50) value of 0.059 mg kg(-1), indicating that it was orally active, but did not inhibit lipopolysaccharide-induced prostaglandin (PG) E(2) production derived by COX-2. Oral administration of FR122047 showed a dose-dependent anti-inflammatory effect in rat CIA with ED(50) value of 0.56 mg kg(-1). This drug also dose dependently suppressed the levels of PGE(2) and TXB(2) in CIA rat paws with ED(50) values of 0.24 and 0.13 mg kg(-1), respectively. FR122047 had no effect in rat AIA model. In contrast, indomethacin, a non-selective COX inhibitor, was anti-inflammatory and reduced the formation of PGs in AIA rat paws. Unlike indomethacin, chronic treatment of FR122047 did not damage the stomach mucosa in CIA rats. These results demonstrate that COX-1 contributes to the oedema and the formation of PGE(2) and TXB(2) in rat CIA model, but not in rat AIA model. We conclude that FR122047 has an orally active and anti-inflammatory effect mediated by inhibition of PGE(2) and TXB(2) produced by COX-1 at a site of inflammation induced by type II collagen and it may be a useful tool for studying the involvement of COX-1 in various in vivo models of inflammation.

Topics: Adjuvants, Immunologic; Animals; Arthritis, Experimental; Chronic Disease; Collagen; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Dinoprostone; Dose-Response Relationship, Drug; Edema; Female; Hindlimb; Isoenzymes; Membrane Proteins; Piperazines; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Inbred Lew; Thiazoles; Thromboxane B2

The aim of the present study was to characterize during acute and chronic liver injury induced by CCl4, macrophage phenotypes and whether a change in reactive oxygen intermediates (ROI) and eicosanoids production by Kupffer cells (KC) was observed.. Liver steato-necrosis and cirrhosis were induced in rats after 3 weeks and 9 weeks of CCl4 intoxication, respectively. Monocytes and tissue macrophages were identified by immunohistochemical study using monoclonal antibodies ED-1 and tissue macrophages using the antibody ED-2. The release of ROI and eicosanoids in response to the phorbol ester TPA (protein kinase activator) and to the calcium ionophore A23187 was assessed in cultivated cells.. As compared to healthy controls, livers of rats with steato-necrosis or cirrhosis exhibited a significant increase of ED-1 and ED-2 positive cells. Only KC from rats with liver steato-necrosis were found to have higher A23187, TPA + A23187 or opsonized zymosan induced ROI production than healthy controls (p < 0.01). After TPA + A23187 or opsonized zymosan stimulation, KC from both rats with steato-necrosis or cirrhosis produced more TxB2 and leukotrienes and less PGE2 as compared to healthy controls (p <0.05).. These results suggest an influx of monocytes into the liver during acute and chronic injury induced by CCl4. Functional changes of this inflammatory infiltrate have been demonstrated with an increase of ROI production only in the early stage of liver injury whereas a rise in KC leukotriene production and an imbalance between cytoprotective and cytotoxic prostanoids were observed at all stages of liver disease.

Topics: Acute Disease; Animals; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Chronic Disease; Eicosanoids; Immunohistochemistry; Kupffer Cells; Macrophages; Male; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Thromboxane B2

Enhanced thromboxane (TX) biosynthesis has previously been reported in the acute phase after ischemic stroke. We investigated whether enhanced urinary excretion of 11-dehydro-TXB2, a noninvasive index of platelet activation, was present in the chronic phase after a transient ischemic attack (TIA) or stroke, including intracerebral hemorrhage.. We obtained a single urinary sample from 92 patients between 3 and 9 months after onset of stroke or TIA. The urinary excretion of the major enzymatic metabolite of TXA2, 11-dehydro-TXB2, was measured by a previously validated radioimmunoassay. The excretion rates were compared with those of 20 control patients with nonvascular neurological diseases.. Urinary 11-dehydro-TXB2 averaged 294+/-139, 413+/-419, and 557+/-432 pmol/mmol creatinine for patients with TIA, ischemic stroke, and intracerebral hemorrhage, respectively; the values were higher in all subgroups (P<0.01) than that in control patients (119+/-66 pmol/mmol). Increased 11-dehydro-TXB2 excretion was present in 59% of all patients, in 60% (P<0.001) of patients with TIA, in 56% (P<0.001) of patients with ischemic stroke, and in 73% (P<0.001) of patients with intracerebral hemorrhage. Atrial fibrillation, no aspirin use, and severity of symptoms at follow-up contributed independently to the level of 11-dehydro-TXB2 excretion in a multiple linear regression analysis.. Platelet activation is often present in patients in the chronic phase after stroke, including those with intracerebral hemorrhage. Persistent platelet activation, which is associated with atrial fibrillation and poor stroke outcome, can be substantially suppressed by aspirin treatment.

Topics: Brain Ischemia; Cerebral Hemorrhage; Chronic Disease; Follow-Up Studies; Humans; Platelet Activation; Thromboxane B2

To further study the mechanisms of damages and resorption of bone in chronic periapical periodontitis.. The quantities and distribution of PGE2 and TXB2 in apical granuloma of chronic periapical periodontitis were analyzed using radio immunization analysis.. The quantities of PGE2 and TXB2 in apical granuloma of chronic periapical periodontitis were significantly (P < 0.05) higher than those in controls.. The PGE2 has the close relation with the bone resorption of chronic periapical periodontitis during the whole process. Meanwhile, TXB2 also has certain relation with the bond absorption. The quantities of PGE2 and TXB2 are imbalanced.

Topics: Adolescent; Adult; Bone Resorption; Chronic Disease; Dinoprostone; Female; Granuloma; Humans; Male; Middle Aged; Periapical Periodontitis; Radioimmunoassay; Thromboxane B2

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

The PGE2, PGF2 alpha, PGI2, and TXB2 content in biopsies of healthy esophageal mucosa and inflamed mucosa and from subjects with chronic esophagitis was measured and statistically analyzed. No significant differences were found between the tissue concentrations of prostaglandins in the inflamed and the healthy mucosa, except for elevated PGI2 content in the inflamed esophageal mucosa in comparison to healthy mucosa. The prostaglandin content of jejunal mucosa was unchanged in jejunitis and in atrophy compared to findings in healthy subjects. Regression analysis revealed a significant negative correlation between the PGF2 alpha and PGI2 content in both inflamed esophageal and inflamed jejunal mucosa. In healthy mucosa, no correlation was found between the tissue concentrations of these two prostaglandins, either in the esophagus or in the jejunum. These results suggest the redistribution of cyclic endoperoxide metabolism under certain pathological conditions.

Topics: Analysis of Variance; Biopsy; Chronic Disease; Dinoprost; Dinoprostone; Epoprostenol; Esophagitis; Humans; Intestinal Mucosa; Jejunal Diseases; Linear Models; Mucous Membrane; Prostaglandins; Thromboxane B2

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

To evaluate the effects of a thromboxane inhibitor on the production of eicosanoids by the colonic mucosa of patients with chronic ulcerative colitis.. Fourteen patients with active left-sided ulcerative colitis were divided into in two treatment groups. Seven patients received oral ridogrel (300 mg twice daily) and seven 5-aminosalicylic acid (5-ASA; 1 g twice daily) for 4 weeks. Intracolonic eicosanoid and elastase release were measured using a colonic double-lumen perfusion technique. An isotonic solution was infused 50 cm from the anal verge at the rate of 5 ml/min, and recovered by siphonage 30 cm distally. Effluents were assayed for thromboxane B2 (TXB2), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) by radioimmunoassay (RIA), and for polymorphonuclear elastase by immunoactivation. Clinical and colonoscopic criteria were used to determine activity before and after treatment.. Four of the seven patients in the ridogrel group and five of the seven in the 5-ASA group showed clinical and colonoscopic improvement. Intraluminal elastase release decreased in every responding patient in the 5-ASA group (P < 0.05) and in three out of seven responders in the ridogrel group. Basal eicosanoid release was similar in both groups. In the responders, 5-ASA significantly reduced the release of the three eicosanoids (P < 0.05). Ridogrel reduced the release of TXB2 to 31% of basal levels (P < 0.01) but the release of PGE2 and LTB4 was not affected.. These results suggest that ridogrel is an oral active selective inhibitor of thromboxane synthetase, which modifies the pattern of colonic eicosanoid generation in patients with chronic ulcerative colitis. Oral ridogrel may be a useful treatment for patients with non-severe ulcerative colitis, although specific indications require further studies.

Topics: Adult; Aged; Aminosalicylic Acids; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Colitis, Ulcerative; Colon; Dinoprostone; Female; Humans; Intestinal Mucosa; Leukotriene B4; Male; Mesalamine; Middle Aged; Pancreatic Elastase; Pentanoic Acids; Pyridines; Thromboxane B2; Thromboxane-A Synthase

We evaluated regional blood flows in a hyperdynamic sepsis model and the reversal of increased flows by blockade of nitric oxide (NO) synthase. Seven awake sheep were continuously infused with Escherichia coli endotoxin [lipopolysaccharide (LPS), 10 ng.kg-1.min-1] for 48 h. The NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg) was injected after 24 h. Blood flows to systemic organs were determined with the radioactive microsphere technique. LPS induced elevation of cardiac index by 36% (P < 0.05) and a fall in systemic vascular resistance index by 37% (P < 0.05) at 0 h [time of L-NAME administration, 24 h after infusion of LPS had begun] L-NAME administration normalized cardiac index [6.1 +/- 0.5 at 4 h posttreatment, 6.1 +/- 0.5 l.min-1.m-2 at -24 h (baseline)] and systemic vascular resistance index (1,333 +/- 105 at 4 h posttreatment, 1,280 +/- 163 dyn.s.cm-5.m2 at -24 h) and reduced all regional blood flows to near-baseline levels for the remainder of the study period (24 h). O2 consumption was unaffected by treatment.

Topics: Amino Acid Oxidoreductases; Animals; Arginine; Blood Pressure; Cardiac Output; Chronic Disease; Escherichia coli; Female; Lactates; Lactic Acid; Lipopolysaccharides; Microspheres; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Regional Blood Flow; Sheep; Thromboxane B2; Toxemia; Vascular Resistance; Vasodilation

Serum cortisol levels and bronchoalveolar lavage fluid (BALF) from 105 patients with chronic obstructive pulmonary disease (COPD) and 36 normal subjects were examined and the relationship between cortisol inhibiting the TXB2 secreted by alveolar macrophage (AM) and the theory of Syndrome Differentiation in TCM was explored. Results showed: (1) No significant differences were found between chronic bronchitis and normal subjects on cortisol levels in serum, but in BALF, cortisol levels was significantly lower in Lung Qi Deficiency when compared with that in normal subjects. (2) the levels of cortisol inhibiting the TXB2 secreted by AM which were significantly lower in chronic bronchitis when compared with that in control. In short, the amount and function of cortisol in BALF were significantly different in various syndromes in TCM of chronic bronchitis.

Topics: Adult; Aged; Bronchitis; Bronchoalveolar Lavage Fluid; Chronic Disease; Diagnosis, Differential; Female; Humans; Hydrocortisone; Macrophages, Alveolar; Male; Medicine, Chinese Traditional; Middle Aged; Thromboxane B2; Yin Deficiency

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

1. The role of prostanoids in experimental colitis with trinitrobenzene sulfonic acid (TNBS) in rats was investigated. The effects of cyclosporine A (CsA) on the development of experimental colitis were also examined. 2. Five kinds of prostanoids were detected in rat colonic tissue by high performance liquid chromatography. These were 6-keto-prostaglandin (PG) F1 alpha, PGF2 alpha, PGE2, PGD2 and thromboxane B2. 3. In TNBS-induced experimental colitis, all prostanoid concentrations except PGD2 increased, although the time courses differed from each other. 4. Medication with indomethacin markedly reduced prostanoid concentrations in TNBS-induced colitis. However, indomethacin did not show any effect on damage scores. 5. Cyclosporine A reduced damage scores 14 days after TNBS treatment, and the protective effects were observed, whereas CsA did not affect colonic tissue prostanoid concentrations. 6. Prostanoids might be produced secondarily in the genesis of TNBS-induced colitis, although they may attenuate the inflammatory response. It was also suggested that CsA was likely to have therapeutic effects on experimental colitis by inhibiting the immune reaction with TNBS, which induced the chronic inflammation.

Topics: Animals; Chromatography, High Pressure Liquid; Chronic Disease; Colitis; Colon; Cyclosporine; Disease Models, Animal; Indomethacin; Male; Prostaglandins; Rats; Rats, Wistar; Thromboxane B2; Trinitrobenzenesulfonic Acid

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

There has been no useful treatments for chronic vascular rejection (CVR) after kidney transplantation until now. Recently, however, some reports have suggested that the thromboxane A2 synthetase inhibitor, OKY-046, is useful in reducing proteinuria in nephrotic syndrome and preventing progression of CVR. Five patients with CVR (serum creatinine range: 1.7-2.6 mg/dl) were treated with OKY-046 for over one year and the effect of OKY-046 was evaluated. One patient developed acute rejection and another renal hypertension during this study. Except for the cases of acute rejection and renal hypertension, serum creatinine slightly decreased in 1 case and remained unchanged in 2 cases. Urinary excretion of protein and thromboxane B2 decreased significantly but prostaglandin E2 did not change in the treatment of the deterioration with OKY-046. We concluded that OKY-046 was effective in preventing graft function and decreasing urinary protein excretion in kidney transplant recipients with CVR.

Topics: Acrylates; Chronic Disease; Female; Graft Rejection; Humans; Kidney; Kidney Transplantation; Male; Methacrylates; Prostaglandins E; Proteinuria; Thromboxane B2; Thromboxane-A Synthase

Data in the literature suggest that cases of hypoalphalipoproteinemia involve an increase in thromboxane B2 (TXB2) together with an increased risk of atherosclerosis. A recent detailed examination of a 32-year-old man revealed clinical and biochemical features strongly indicative of that pathology. The case presented several unusual features: marked infiltration of the skin and mesenteric lymph nodes by histiocytic lipids with sufficient hyperplasia to induce acute intestinal occlusion combined with an in vivo TXB2 generation curve, subsequently inhibited by aspirin, that was comparable to the curves of the control subjects. Furthermore there were no signs of early atherosclerotic damage so that it was possible to postulate the hypothesis that despite the 50% drop in alpha-lipoprotein levels, they were still sufficient to ensure normal turnover of the other lipoproteins so that, however complex the clinical condition, it was an incomplete expression of a phenotype.

Topics: Adult; Arteriosclerosis; Aspirin; Chronic Disease; Histiocytes; Humans; Hypolipoproteinemias; Lipoproteins, HDL; Lymph Nodes; Male; Skin; Thromboxane B2

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

Inhibition of the enzyme that synthesizes thromboxanes may protect against the development of ventricular fibrillation (VF) during acute myocardial ischemia. This study was carried out to test this hypothesis with a new thromboxane synthetase inhibitor, and to extend the studies to alternative animal models of myocardial infarction. In a series of acute experiments, 19 cats were pretreated with 10 mg/kg of U-63557A (a dose that produced greater than 75% reduction in thromboxane B2 [TxB2] levels) or saline before abrupt left anterior descending coronary artery occlusion. Seven of the nine control animals suffered spontaneous VF associated with a 77% fall in VF threshold compared with the treated animals, of which 2 of 10 had spontaneous VF and in which VF threshold fell by only 45% (p less than 0.025). Despite a similar extent of TxB2 inhibition in another set of nine animals, U-63557A failed to protect against a fall in VF threshold during coronary reperfusion. Finally, chronic changes in VF threshold and inducibility of sustained ventricular tachycardia by programmed stimulation were assessed in a group of eight animals. The lowering of VF threshold and inducibility of ventricular tachycardia seen in the control state were not influenced by treatment with U-63557A. Thus protection against infarct-related VF by TxB2 inhibition is a property shared by more than one pharmacologic agent. Arrhythmias generated by reperfusion or induced in a more chronic setting may not be thromboxane-dependent. These results have important implications for the planning of studies designed to assess the antiarrhythmic potential of drugs that inhibit thromboxane synthesis.

Topics: Acute Disease; Animals; Benzofurans; Cardiac Pacing, Artificial; Cats; Chronic Disease; Female; Male; Myocardial Infarction; Myocardial Reperfusion; Thromboxane B2; Thromboxane-A Synthase; Ventricular Fibrillation

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

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Chronic Disease; Estrogens; Female; Hematoma, Subdural; Humans; Kinetics; Male; Middle Aged; Platelet Aggregation; 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

Defective platelet thromboxane synthesis has been described in uraemia and attributed to a 'functional cyclooxygenase defect'. We have studied platelet aggregation and generation of immunoreactive thromboxane B2 (TXB2) in 11 subjects on a chronic haemodialysis programme. The platelet function abnormality of uraemia was confirmed, maximal aggregation in response to collagen (2 and 4 micrograms/ml) and sodium arachidonate (1.5 and 3.0 mM) being significantly depressed. However, increased platelet aggregation in response to sodium arachidonate 0.75 mM was noted. Due to the reduced haematocrit, the platelet concentration in platelet-rich plasma (PRP) of uraemic subjects was significantly lower than that of controls; when TXB2 generation in PRP adjusted to 200 X 10(9) platelets/l was assessed, no evidence for a defect of cyclooxygenase was found, although reduced synthesis of TXB2 in response to thrombin was noted. Furthermore, increased thromboxane generation by uraemic PRP in response to sodium arachidonate 0.75 mM was detected. We conclude that the mild platelet abnormality in uraemic subjects treated by haemodialysis is not explained by a 'functional cyclooxygenase defect', although an abnormality of thrombin-induced thromboxane synthesis may be present. Furthermore, the tendency to increased aggregation and thromboxane synthesis in response to a low concentration of arachidonic acid may contribute to the thrombotic tendency which is also described in such subjects.

Topics: Adult; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Chronic Disease; Collagen; Female; Humans; Male; Platelet Aggregation; Prostaglandin-Endoperoxide Synthases; Renal Dialysis; Thrombin; Thromboxane B2; Uremia

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

We have examined the urinary excretion of stable immunoreactive eicosanoids in 23 female patients with systemic lupus erythematosus (SLE), 16 patients with chronic glomerular disease (CGD), and 20 healthy women. SLE patients had significantly higher urinary thromboxane B2 (TXB2) and prostaglandin (PG) E2 excretion and significantly lower 6-keto-PGF1 alpha than did healthy women. In contrast, CGD patients only differed from controls for having reduced 6-keto-PGF1 alpha excretion. The group of SLE patients with active renal lesions differed significantly from the group with inactive lesions for having a lower creatinine clearance and urinary 6-keto-PGF1 alpha and higher urinary TXB2. Higher urinary TXB2 excretion was associated with comparable platelet TXB2 production in whole blood, undetectable TXB2 in peripheral venous blood, and unchanged urinary excretion of 2,3-dinor-TXB2. A significant inverse correlation was found between urinary TXB2 and creatinine clearance rate (CCr). In contrast, the urinary excretion of 6-keto-PGF1 alpha showed a significant linear correlation with both CCr and para-aminohippurate clearance rate (CPAH). In four SLE and seven CGD patients, inhibition of renal cyclooxygenase activity by ibuprofen was associated with a significant reduction in urinary 6-keto-PGF1 alpha and TXB2 and in both CCr and CPAH. However, the average decrease in both clearances was 50% lower in SLE patients than in CGD patients, when fractionated by the reduction in urinary 6-keto-PGF1 alpha or PGE2 excretion. We conclude that the intrarenal synthesis of PGI2 and TXA2 is specifically altered in SLE. Such biochemical alterations are associated with changes in glomerular hemodynamics and may play a role in the progression of SLE nephropathy.

Topics: Adolescent; Adult; Aged; Blood Platelets; Chronic Disease; Dinoprost; Dinoprostone; Epoprostenol; Female; Gas Chromatography-Mass Spectrometry; Glomerulonephritis; Humans; Ibuprofen; Kidney; Kidney Function Tests; Lupus Erythematosus, Systemic; Middle Aged; Prostaglandins E; Prostaglandins F; Radioimmunoassay; Thromboxane A2; Thromboxane B2

Topics: Adolescent; Adult; Chronic Disease; Female; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Humans; Male; Middle Aged; Nephrosis, Lipoid; Radioimmunoassay; Thromboxane B2; Thromboxanes

Vasodilatory prostaglandins function to maintain renal perfusion in patients with cirrhosis and ascites. To evaluate the potential contribution of the vasodilator prostaglandin E2 and the vasoconstrictor metabolite thromboxane B2 to the development of the hepatorenal syndrome, we measured urinary excretion of these products in 14 patients with hepatorenal syndrome and in control populations with acute or chronic liver or kidney failure. Radioimmunoassay measurements were confirmed by bioassay and by mass spectrometry. Prostaglandin E2 was decreased compared with healthy controls (2.2 +/- 0.3 vs. 6.3 +/- 0.8 ng/h, p less than 0.01) and compared with acute renal failure (9.6 +/- 2.1 ng/h) and with alcoholic hepatitis (9.2 +/- 3.3 ng/h). Thromboxane B2 concentration was normal in patients with alcoholic hepatitis (0.12 +/- 0.02 vs. 0.15 +/- 0.03 ng/ml) and minimally increased in acute renal failure (0.18 +/- 0.15 ng/ml), but markedly elevated in hepatorenal syndrome (0.69 +/- 0.15 ng/ml, p less than 0.001). Urinary thromboxane B2 concentration fell with improved renal function in 3 patients who survived. These data suggest an imbalance of vasodilator and vasoconstrictor metabolites of arachidonic acid in patients with the hepatorenal syndrome.

Topics: Acute Disease; Acute Kidney Injury; Adolescent; Adult; Biological Assay; Chronic Disease; Dinoprostone; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Liver Diseases; Male; Mass Spectrometry; Middle Aged; Prostaglandins E; Radioimmunoassay; Syndrome; Thromboxane B2; Thromboxanes

In recipients of renal transplants, the biochemical defect(s) that underlies increased deposition of platelets in the graft and their shortened survival in the circulation are poorly understood. Forty-six recipients of kidney allografts, with and without rejection signs (13 acute rejections (ARs), 15 chronic rejections (CRs), and 18 functioning transplants (FTs), had lower platelet serotonin (5HT) and higher plasma beta-thromboglobulin than normal controls (NCs). These abnormalities were more pronounced in patients with ARs than with CRs but were also present in patients with FTs. All groups of transplant recipients showed an abnormal metabolism of platelet arachidonate, as expressed by low serum levels of thromboxane B2. In AR, plasma fibrinopeptide A (FPA) was significantly high whereas FPA levels were unchanged in CR and in FT. These findings suggest that in patients with renal transplants, the platelet release reaction has occurred in vivo, resulting in the secretion of granule-bound substances and the circulation of partially empty platelets. Vasoactive, mitogenic, and proaggregatory substances released from platelets might damage the graft and aggravate the rejection process.

Topics: Acute Disease; Adolescent; Adult; beta-Thromboglobulin; Blood Platelets; Cell Survival; Child; Chronic Disease; Female; Fibrinopeptide A; Graft Rejection; Humans; Kidney Transplantation; Male; Middle Aged; Platelet Count; Serotonin; Thromboxane B2

We observed several patients with chronic idiopathic thrombocytopenic purpura (ITP) whose bleeding times were more prolonged than would have been expected from their platelet counts. To investigate this further, we performed in vivo and in vitro platelet function studies, assessed arachidonate metabolism, and measured platelet-associated IgG (PAIGG) in seven patients with chronic ITP. The bleeding times of three of the patients were prolonged for greater than 7 min, and all of these patients had impaired platelet aggregation and abnormal platelet arachidonic acid metabolism as reflected by increased production of the lipoxygenase product HETE and a concomitant decrease in cyclooxygenase products, TXB2 and HHT (p less than 0.001). The abnormalities noted were not due to concomitant drug ingestion, since they were present on repeated evaluation. There was no relationship between the platelet count and the bleeding time; however, there was a significant inverse correlation between the bleeding time and TXB2 production in all patients evaluated (r = 0.81; p less than 0.05). There was no relationship between the level of platelet-associated IgG and any parameter of platelet aggregation or arachidonate metabolism. The abnormalities noted should be looked for in the individual patient with chronic ITP, since the bleeding tendency is exacerbated by the superimposed impairment of platelet function even at platelet counts of greater than 50,000/cu mm, levels generally regarded as "safe."

Topics: Adolescent; Adult; Arachidonic Acids; Bleeding Time; Blood Platelets; Chronic Disease; Humans; Immunoglobulin G; Lipoxygenase; Middle Aged; Platelet Aggregation; Platelet Count; Prostaglandin-Endoperoxide Synthases; Purpura, Thrombocytopenic; Thromboxane B2