thromboxane-b2 and Acute-Disease

The aim of this study was to determine the extent of change in platelet and coagulation markers in the acute phase of ischemic stroke and to assess the utility of marker measurement in stroke subtype classification. Urinary 11-dehydro-thromboxane B(2) (11-dTXB2), a marker of in vivo platelet activation, and markers of coagulation activation, including prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), and fibrinogen, were measured in 25 patients with ischemic stroke within 24 h of onset of symptoms. Marker levels in patients with ischemic stroke were compared with those in 19 age-matched controls who had not taken aspirin for at least 2 weeks before sampling and 25 healthy controls. Median marker levels were significantly increased in stroke over those in age-matched controls for fibrinogen (344 vs. 289 mg/dl; P=0.030), F1+2 (1.40 vs. 0.80 nmol/l; P=0.003), and TAT (6.65 vs. 2.20 microg/l; P<0.0001). Median marker levels for seven patients with cardioembolic stroke and 18 with non-cardioembolic stroke were not significantly different for any marker test. Eight patients taking aspirin at the time of the stroke had significantly lower 11-dTXB2 values than patients not taking aspirin (964 vs. 4,314 pg/mg of creatinine; P=0.007). Stroke patients not taking aspirin had significantly higher 11-dTXB2 concentration than age-matched controls (4,314 vs. 1,788 pg/mg of creatinine; P=0.006). Coagulation and platelet activation markers are increased in the acute phase of stroke regardless of the clinical mechanism. This finding suggests that the markers may not be useful for predicting clinical subtype of ischemic stroke in the acute phase.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Aspirin; Biomarkers; Blood Coagulation; Brain Ischemia; Fibrinogen; Humans; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Stroke; Thromboxane B2

Heavy binge drinking may trigger the onset of embolic stroke and acute myocardial infarction, but the underlying mechanisms are unclear. The effects of binge drinking on the hemostatic system and its circadian variation have not been investigated. We investigated the effects of an acute intake of a large dose of alcohol (1.5 g/kg).. Twelve healthy, nonsmoking men participated in sessions where they were served ethanol in fruit juice or served fruit juice alone and, lying in a supine position, were followed up for 12 to 24 hours. The treatments were randomized and separated from each other by a 1-week washout period. Blood and urine were collected for hemostatic measurements.. The urinary excretion of the platelet thromboxane A(2) metabolite 2, 3-dinor-thromboxane B(2) was significantly (P<0.05) greater during the night after an evening intake of alcohol than during the control night. A smaller increase was observed during the daytime after an intake of alcohol in the morning. The effects on the endothelial prostacyclin metabolite 2,3-dinor-6-ketoprostaglandin F(1alpha) excretion were negligible. A 7-fold increase in plasminogen activator inhibitor 1 activity was observed after both morning (P<0. 05) and evening (P<0.01) intakes of alcohol.. This is the first study to suggest that acute ingestion of a relatively large but tolerable dose of alcohol transiently enhances thromboxane-mediated platelet activation. The observations also demonstrate alcohol-induced changes in the normal circadian periodicity of the hemostatic system in subjects not accustomed to consumption of alcohol.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adult; Alcoholic Intoxication; Biomarkers; Circadian Rhythm; Creatinine; Cross-Over Studies; Disease Susceptibility; Drug Administration Schedule; Ethanol; Fibrinolysis; Hemorheology; Hemostasis; Humans; Male; Myocardial Infarction; Plasminogen Activator Inhibitor 1; Platelet Activation; Platelet Aggregation; Stroke; Supine Position; Thromboxane B2

To study the therapeutic mechanism of Yinchen Dandao decoction (YCDDD) in treating acute cholangitis.. Twenty-four patients with acute cholangitis and 36 cholangiolithiasis patients were randomly classified into the treated group and the control group, and all of these patients had undergone surgical operation. The treated group were given orally YCDDD 3 days after operation for 1 week, and plasma fibronectin (FN), biliary thromboxane A2(TXA2) and prostaglandin I2(PGI2) were measured and compared before and after oral administration of the drug. The models of cholangitis were established in rabbits, which were also randomly grouped into the treated group and the control group, and the same parameters (FN, TXA2, PGI2) were observed as in rabbits.. The level of FN was significantly lower in cholangitis patients than that in the cholangiolithiasis patients before operation (P < 0.01), and compared to the control group, it obviously raised after YCDDD treatment (P < 0.01), the same happened in the cholangiolithiasis patients. The value of TXA2 and PGI2 in the bile was obviously higher (P < 0.01, P < 0.05) in cholangitis patients than those in chlangiolithiasis, and obviously reduced after YCDDD administration (P < 0.01). The level of FN in the treated group and the level of biliary TXA2 and PGI2 in rabbits with cholangitis were significantly higher than those in the control group (P < 0.01).. YCDDD caused the increase of FN and decrease of biliary TXA2 and PGI2, which might be one of the mechanisms of the drug carried out in cholangitis patients.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adult; Animals; Bile; Cholangitis; Drugs, Chinese Herbal; Epoprostenol; Female; Fibronectins; Humans; Male; Middle Aged; Phytotherapy; Rabbits; Random Allocation; Thromboxane B2

Severe acute pancreatitis is a serious disease, but its detailed mechanism has not yet been elucidated. We aimed to clarify the interaction between neutrophils and platelets in the pathogenesis of acute pancreatitis.. We induced acute pancreatitis in rats by injection of sodium taurocholate into the biliopancreatic duct and killed them over time. We observed the histological changes in pancreatic tissue with special attention to the dynamics of neutrophils and platelets. We also measured the concentrations of neutrophil- and platelet-derived factors in pancreatic tissue and blood samples.. Neutrophils and platelets in the pancreatic tissue showed a similar pattern of migration. They initially spread in the interlobular connective tissue and finally into the lobules. The concentration of myeloperoxidase gradually increased in the inflamed pancreas until 24 hours and the concentration of thromboxane B2, plasminogen activator inhibitor 1, and CD41 also increased with time. Finally, the concentration of serum myeloperoxidase, citrullinated histone H3, and high-mobility group box 1 increased over time.. The interaction between neutrophils and platelets in pancreatic tissue plays an important role in the mechanism of advancing severity in acute pancreatitis. Circulating damage-associated molecular patterns induced by excessive local inflammation may lead to other organ injuries.

Topics: Acute Disease; Animals; Blood Platelets; Cell Communication; Disease Progression; HMGB1 Protein; Leukocyte Count; Male; Neutrophils; Pancreas; Pancreatitis; Peroxidase; Platelet Count; Rats, Wistar; Taurocholic Acid; Thromboxane B2

Zhi-Xiong Capsules (ZXC) involving Hirudo, Ligusticum chuanxiong, Salvia miltiorrhiza, Leonurus artemisia, and Pueraria lobata, is an empirical prescription used in Chinese clinics applied for treating cerebral arteriosclerosis and blood-stasis in clinic. However, the mechanism of its antithrombotic activity has not been investigated until now. The present study was designed to investigate its antithrombotic effects, the mechanism of ZXC on anti-thrombus action and to identify the main chemical composition of ZXC using HPLC-DAD-ESI-IT-TOF-MS. Two animal models were used to evaluate the antithrombotic effect of ZXC, the arterial thrombosis model and a venous thrombosis model. ZXC prolonged the plasma recalcification time (PRT), the activated partial thromboplastin time (APTT), the thrombin time (TT) and the prothrombin time (PT) and clearly reduced the content of fibrinogen (FIB) obviously in the arterial thrombosis model. Furthermore, it markedly suppressed the level of TXB

Topics: Acute Disease; Animals; Anticoagulants; Antithrombins; Aspirin; Blood Coagulation; Capsules; Carotid Arteries; Chlorides; Disease Models, Animal; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Ferric Compounds; Fibrinolysis; Heparin; Lung; Mice; Platelet Activation; Platelet Aggregation; Prostaglandins F; Pulmonary Embolism; Rabbits; Rats, Sprague-Dawley; Thrombolytic Therapy; Thrombosis; Thromboxane B2

Urinary 11-dehydro-thromboxane (TX)B2 has been described as a potential predictive biomarker of major adverse cardiovascular events (MACEs) in high cardiac risk patients. This part of LTIMI (Leukotrienes and Thromboxane In Myocardial Infarction) study aimed to evaluate the relationship between 11-dehydro-TXB2 and MACEs in patients with acute myocardial infarction (AMI).. LTIMI was an observational, prospective study in 180 consecutive patients with AMI type 1 referred for primary percutaneous coronary intervention. On admission and at follow-up visits (1 month, 1 year), 11-dehydro-TXB2 was measured in urinary samples by using high-performance liquid chromatography-tandem mass spectrometry. The primary outcome was occurrence of composite MACEs during 1-year after AMI. Left ventricular ejection fraction was assessed in echocardiography on admission and at 1-year follow-up. Analyses of 11-dehydro-TXB2 (pg/mg creatinine) were performed on log-transformed data and expressed as median with IQR (Q1-Q3). 11-Dehydro-TXB2 level on admission was 7.39 (6.85-8.01) and decreased at 1 month (6.73, 6.27-7.12; P<0.001) and 1-year follow-up (6.37, 5.91-6.94; P<0.001). In univariate analysis, baseline 11-dehydro-TXB2 was higher in patients with MACEs (n=60; 7.73, 7.07-8.60) compared with those without MACEs (n=119; 7.28, 6.68-7.79; P=0.002). In multivariate regression model, 11-dehydro-TXB2 and 3 other variables (diabetes, multivessel disease, and left ventricular ejection fraction) were found to be best 1-year cumulative MACE predictors with odds ratio for 11-dehydro-TXB2 of 1.58 (95% CI 1.095-2.33; P=0.017) and area under the curve (in receiver operating characteristic analysis of 0.8). Baseline 11-dehydro-TXB2 negatively correlated with both left ventricular ejection fraction on admission (R=-0.21; P=0.006) and after 1 year (R=-0.346; P<0.001).. 11-Dehydro-TXB2 predicts 1-year cumulative MACEs in AMI patients and provides prognostic information on the left ventricular performance.

Topics: Acute Disease; Aged; Biomarkers; Echocardiography; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Prognosis; Prospective Studies; Stroke Volume; Thromboxane B2; Time Factors

The Wistar-Furth (WF) rat strain is usually used in models of full major histocompatibility complex-mismatched kidney transplantation. Because these rats have been demonstrated to be resistant to several models of chronic kidney disease, the aim of the present study was to investigate their potential resistance to renal ischaemia-reperfusion (I/R) injury compared with another strain, namely Wistar-Hanover (WH) rats. Anaesthetized male WH and WF rats were submitted to I/R by occlusion of the left renal artery and contralateral nephrectomy. Urine, blood and tissue samples were collected at different time points after I/R to evaluate renal function, inflammation and tubular injury, along with determination of nitric oxide synthase (NOS) expression and thromboxane A2 (TxA2 ) production. Post-ischaemic renal function was better preserved in WF than WH rats, as evidenced by reduced levels of creatininaemia, urinary neutrophil gelatinase-associated lipocalin excretion and proteinuria. In addition, WF rats had less intrarenal inflammation than WH rats after I/R injury. These observations were associated with maintenance of neuronal NOS expression, along with lower induction of inducible NOS expression in WF versus WH rats. Moreover, WF rats excreted a significantly lower amount of TxB2 . The results indicate that WF rats are more resistant to an I/R injury than WH rats in terms of renal function and inflammation. These observations are associated with differential regulation of intrarenal NOS expression, as well as a reduction in thromboxane production, which could contribute to a better outcome for the postischaemic kidney in WF rats.

Topics: Acute Disease; Animals; Dinoprostone; Disease Models, Animal; Kidney; Kidney Function Tests; Male; Nitric Oxide; Nitric Oxide Synthase; Oxidative Stress; Rats, Inbred WF; Real-Time Polymerase Chain Reaction; Reperfusion Injury; Reverse Transcriptase Polymerase Chain Reaction; Thromboxane A2; Thromboxane B2

Aspirin is the most commonly used antiplatelet drug for prevention of ischaemic stroke. In order to determine the prevalence and nature of aspirin failure, we studied 51 adults admitted with suspected ischaemic stroke and already prescribed daily aspirin. Within 48 hours (h) of onset, blood and urine samples were collected to assess platelet aggregation, activation and aspirin response by a range of methods. All tests were then repeated on a second sample taken 24 h after witnessed administration of 75 mg or 150 mg aspirin. At entry to the study, incomplete response to aspirin, measured by arachidonic acid (AA)-stimulated platelet aggregation, was found in 43% of patients. Following in-hospital aspirin administration, there was a significant decrease in AA-aggregation (p=0.001) suggesting poor adherence to therapy prior to admission. However, residual aggregation (10-15%) persisted in 11 subjects - suggesting alternative causes. In incomplete responders on admission, platelet aggregation with adenosine diphosphate (ADP) was significantly higher compared with responders (p<0.05) but there were no significant differences in collagen aggregation, platelet fibrinogen binding or P-selectin expression, plasma von Willebrand factor, fibrinogen, high-sensitivity C-reactive protein, or the urinary metabolite, 11-dehydro-TxB2. Incomplete platelet inhibition is common around the time of acute cerebrovascular ischaemic events in patients prescribed aspirin. Up to 50% of these observations appear due to incomplete adherence to aspirin therapy. Intervention studies are required to determine the clinical relevance of measured platelet response to aspirin in terms of outcome, and the effectiveness of improved pharmacotherapy for stroke prevention.

Topics: Acute Disease; Aged; Aged, 80 and over; Arachidonic Acid; Aspirin; Brain Ischemia; Drug Resistance; Female; Humans; Male; P-Selectin; Patient Compliance; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Thromboxane B2

The aim of the present study was to investigate whether pentoxifylline (PTX) treatment could protect against induced acute radiation enteritis.. Rats received 100 mg/kg/day PTX for 7 days before irradiation and continued on treatment for 3 days after irradiation. The intestinal myeloperoxidase (MPO) activities and malondialdehyde (MDA), glutathione (GSH), prostaglandin E2, and thromboxane B2 levels were determined. Terminal ileum tissue was evaluated for morphological changes. Also, nuclear factor kappa (NF-kappa), tumor necrosis factor-alpha (TNF-alpha), and intercellular adhesion molecule 1 (ICAM-1) expressions were analyzed with immunohistochemisty methods.. PTX treatment was associated with increased GSH levels and decreased MPO activity and MDA, prostaglandin E2, and thromboxane B2 levels. Histopathologic examination showed that intestinal mucosal structure was preserved in the PTX-treated group while having significant decreases in NF-kappaB, TNF-a, and ICAM-1 expression.. PTX appears to have a protective effect against radiation damage. This protective effect is mediated in part by decreasing both inflammatory reactions and oxidative stress.

Topics: Acute Disease; Animals; Dinoprostone; Enteritis; Glutathione; Ileum; Immunohistochemistry; Intercellular Adhesion Molecule-1; Male; Malondialdehyde; NF-kappa B; Pentoxifylline; Peroxidase; Radiation Injuries, Experimental; Radiation-Protective Agents; Rats; Rats, Wistar; Thromboxane B2; Tumor Necrosis Factor-alpha

The use of cyclooxygenase-2 (COX-2) inhibitors has been reported to be associated with detrimental vascular events. The aim of our study was to evaluate the role of COX-2 activity in the control of human vascular tone under inflammatory conditions.. Using organ bath experiments, the contraction induced by norepinephrine (NE), U46619, acetylcholine, and KCl was performed on isolated human internal mammary arteries (IMA) cultured in the presence or absence of both interleukin-1beta (IL-1beta) and lipopolysaccharide (LPS) with or without endothelium. Under these conditions the COX (cyclooxygenase) isoforms were detected by immunohistochemistry and western blot, and the prostaglandins (PG) and thromboxane (Tx) released were measured using an enzyme immunoassay kit. A significant decrease in the maximal effect induced by NE but not by other stimuli was observed in the IL-1beta- and LPS-treated preparations after 6 and 24 h of culture (-19 +/- 6 and -25 +/- 4%, respectively), an effect that was endothelium independent. Under this inflammatory condition, the COX-2 inhibitors DFU (1 micromol/L), DuP-697 (0.5 micromol/L), and Etoricoxib (1 micromol/L) markedly restored and increased the vascular reactivity to NE. These alterations were not observed with SC-560 (1 micromol/L), a selective COX-1 inhibitor. In addition, the COX-1 isoform was always detected and the COX-2 isoform was only found in human IMA exposed for 6 or 24 h under inflammatory conditions. The COX-2 induction was accompanied by an increase in PGE(2) (prostaglandin E(2)) and PGI(2) (prostaglandin I(2)) release in the culture medium (approximately 2.5-fold) but not with an increase in TxA(2) (thromboxane A(2)) release.. These observations suggest that the inhibition of COX-2 directly potentiates the human vascular tone induced by NE under inflammatory conditions.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Aged; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dinoprostone; Endothelium, Vascular; Female; Humans; Inflammation; Interleukin-1beta; Lipopolysaccharides; Male; Middle Aged; Norepinephrine; Organ Culture Techniques; Thromboxane B2; Vasoconstriction

To investigate the effect of bacailin on inflammatory mediators and microcirculation disturbance in severe acute pancreatitis (SAP) rats and explore its therapeutic mechanism.. The rats were randomly divided into SAP group, baicalin-treated group and sham operated group. At 3, 6, and 12 hours after operation, we examined the mortality rate of rats, ascites volume, and pancreatic pathological changes in each group and determined the contents of inflammatory mediators in blood as well as the changes in blood viscosity.. Compared with SAP group, treatment with baicalin is able to improve the pathological damage of the pancreas, reduce the contents of multiple inflammatory mediators in blood, decrease the amount of ascitic fluid, and reduce the mortality rates of SAP rats. The low-shear whole blood viscosity in baicalin-treated group (at 3 hours) as well as the high-shear and low-shear whole blood viscosity in baicalin-treated group (at 12 hours) were significantly lower than that in SAP group.. Baicalin has good prospects in the treatment for SAP because it can exert therapeutic effects on this disease through inhibiting the production of inflammatory mediators, decreasing blood viscosity, improving microcirculation, and mitigating the pathological damage of the pancreas.

Topics: Acute Disease; Amylases; Animals; Anti-Inflammatory Agents, Non-Steroidal; Ascites; Dinoprostone; Flavonoids; Inflammation Mediators; Interleukin-1beta; Male; Microcirculation; Pancreas; Pancreatitis; Phospholipases A2; Platelet Activating Factor; Random Allocation; Rats; Rats, Sprague-Dawley; Thromboxane B2

Eighty patients were studied at the first day of the development of lacunar stroke, the main attention being focused on the particular form of focal pathology--a small deep (lacunar) stroke (SDS). Patients with arterial hypertension and complication free course had higher hemorheologic parameters (blood viscosity, erythrocytes aggregation) and a shift of prostacyclin-thromboxane balance towards preaggregation and decrease of fibrinolysis. These disturbances strengthened during the development of SDS. The endothelium dysfunction, alterations of blood rheologic characteristics due to the formation of aggregants of erythrocytes, decrease of erythrocytes deformation and activation of cell homeostasis play a central role in the development of intracranial arterial occlusion resulted in the SDS development. At the same time, fibrinolysis remains relatively stable.

Topics: Acute Disease; Adult; Blood Viscosity; Brain Infarction; Disease Progression; Epoprostenol; Erythrocyte Aggregation; Fibrinolysis; Follow-Up Studies; Homeostasis; Humans; Middle Aged; Prognosis; Radioimmunoassay; Risk Factors; Thromboxane B2

Elevated levels of 11-dehydrothromboxane B2 (11-dehydro-TXB2) excreted in urine have been observed in acute ischemic stroke. This marker of platelet activation has not been investigated in patients with acute spontaneous intracerebral hemorrhage (ICH).. We examined 43 patients with spontaneous ICH and 23 controls. Urinary excretion rates of 11-dehydro-TXB2, 2,3-dinor-thromboxane B2 (2,3 dinor-TXB2) and 2,3-dinor-6-ketoprostaglandin F(1alpha) (2,3-dinor-PGF(1alpha)) during the first week and at 3 months after ICH were compared between patients who had or had not used aspirin and controls.. On admission, ICH patients without aspirin use had significantly higher urinary levels of 11-dehydro-TXB2 (p<0.001), 2,3-dinor-TXB2 (p<0.001) and 2,3-dinor-PGF(1alpha) (p=0.019) than controls. Aspirin users had significantly lower urinary levels of these metabolites than nonusers. The metabolite levels of aspirin users on admission did not significantly differ from those of controls. The differences between aspirin users and nonusers leveled off during the following 3-5 days, however, as the blocking effect of aspirin on the production of TXA2 and PGI2 ceased. Three months after ICH, the metabolite excretion levels in all the patients were similar to those in nonusers of aspirin on admission. On admission, aspirin users had longer bleeding times (p=0.032) than nonusers, but aspirin use did not associate with impaired recovery or hematoma enlargement.. Urinary excretion levels of 11-dehydro-TXB2, 2,3-dinor-TXB2 and 2,3-dinor-PGF1alpha were higher in patients with acute ICH than in controls. The levels in aspirin users were equally low as in controls but rose to the levels of the other patients within a few days. The metabolite levels remained high 3 months after ICH in all patients. Prior use of aspirin did not seem to cause hematoma enlargement.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Aged; Aspirin; Bleeding Time; Blood Coagulation; Cerebral Hemorrhage; Epoprostenol; Female; Humans; Male; Middle Aged; Prospective Studies; Regression Analysis; Thromboxane A2; Thromboxane B2

This study was undertaken to clarify the effects of propofol on endotoxin-induced acute lung injury. Rabbits were randomly assigned to one of four groups. Each group received intravenous infusion of saline only, saline and Escherichia coli endotoxin, propofol (1 mg/kg bolus, then 5 mg/kg/hr) and endotoxin, or propofol (4 mg/kg bolus, then 20 mg/kg/hr) and endotoxin respectively. Infusion of saline or propofol was started 0.5 hr before the infusion of saline or endotoxin, and continued for 6 hr thereafter. The lungs of rabbits were ventilated with 40% oxygen. Mean blood pressure, heart rate, arterial oxygen tension (PaO2), and peripheral blood leukocyte and platelet count were recorded. The wet/dry (W/D) weight ratio of lung and lung injury score were measured, and analysis of bronchoalveolar lavage fluid (BALF) was done. Endotoxin decreased PaO2, and peripheral blood leukocyte and platelet count. And it increased W/D ratio of lung, lung injury score and leukocyte count, percentage of PMN cells, concentration of albumin, thromboxane B2 and IL-8 in BALF. Propofol attenuated all these changes except the leukocyte count in peripheral blood. In conclusion, propofol attenuated endotoxin-induced acute lung injury in rabbits mainly by inhibiting neutrophil and IL-8 responses, which may play a central role in sepsis-related lung injury.

Topics: Acute Disease; Albumins; Anesthetics, Intravenous; Animals; Blood Platelets; Blood Pressure; Bronchoalveolar Lavage Fluid; Endotoxins; Escherichia coli; Free Radical Scavengers; Interleukin-8; Leukocytes; Lung; Lung Injury; Male; Organ Size; Oxygen; Propofol; Rabbits; Sepsis; Sodium Chloride; Thromboxane B2; Time Factors

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

A tissue chamber model of acute inflammation for use in comparative studies in calves, sheep, goats and pigs has been established and validated. Tissue chambers were prepared from silicon rubber tubing, of inner diameter 12.7 mm, length 115 mm and volume 15 ml, with 10 holes, each of 6mm diameter, at each end. In each animal two or four chambers were inserted at subcutaneous sites. Six weeks after implantation an acute inflammatory reaction in a single cage was generated by the intracaveal injection of 0.5 ml of 1% carrageenan solution. Serial samples of exudate (injected chamber), transudate (non-injected chamber) and blood were collected for measurement of exudate and transudate leucocyte count, prostaglandin (PG)E(2) concentration in exudate and serum thromboxane (Tx)B(2) concentration. In addition, skin temperature changes over exudate and transudate chambers were recorded. In all four species, carrageenan induced an acute inflammatory response, indicated by increases to peak values followed by return towards baseline in skin temperature, leucocyte count and PGE(2) concentration. For each of these variables in calves, sheep and goats the increases were significantly greater for exudate than for transudate. The degree of intra-species variation in each variable was acceptable. Marked inter-species differences were recorded: skin temperature rise was greatest in calves and least in sheep and goats; exudate PGE(2) concentration was increased in the order sheep>goat>pig>calf; serum TxB(2) concentration was increased in the order calf>goat>sheep>pig and exudate leucocyte count was increased to a greater extent in the pig than in the three ruminant species. The model has advantages over some previously described tissue chamber models of inflammation and will be suitable for use in comparative studies of inflammatory mechanisms and the pharmacokinetics and pharmacodynamics of anti-inflammatory drugs.

Topics: Acute Disease; Animals; Body Temperature; Cattle; Diffusion Chambers, Culture; Dinoprostone; Exudates and Transudates; Female; Goats; Inflammation; Leukocyte Count; Leukocytes; Male; Sheep, Domestic; Species Specificity; Swine; Thromboxane B2; Time Factors

The influence of platelet von Willebrand factor (vWF)-glycoprotein (GP)Ib-V-IX and GPIIb-IIIa receptor interactions in the context of hyperacute rejection (HAR) of pulmonary xenografts has not previously been explored.. Aurintricarboxylic acid (ATA, an inhibitor of platelet-GPIb interactions with vWF), SC52012A (SC, a synthetic GPIIb/IIIa inhibiting peptide), or both were added to heparinized whole human blood before perfusion of isolated piglet lungs. Results were compared with unmodified blood ("unmodified").. Perfusion of porcine lungs with unmodified human blood resulted in an immediate rise in pulmonary vascular resistance (PVR), fluid and platelet sequestration in the lung, and, without exception, cessation of function within 15 minutes with a mean survival of 8 minutes. Addition of ATA or SC before lung perfusion significantly decreased the rise in PVR, diminished histamine release, and prolonged survival to 31+/-11 and 31+/-22 minutes, respectively. When the therapies were combined, mean survival was 156+/-77 minutes (P<0.05 vs. either monotherapy). Complement activation was synergistically attenuated only when the drugs were used together.. Platelet protein receptor adhesive interactions play an important role in amplification of complement activation during hyperacute lung rejection. Inhibiting recruitment of platelets at the site of initial immunologic injury to endothelial cells may protect porcine organs against thrombosis and inflammation during the initial exposure to human blood.

Topics: Acute Disease; Animals; Aurintricarboxylic Acid; Blood Physiological Phenomena; Blood Platelets; Complement Activation; Dipeptides; Drug Synergism; Graft Rejection; Graft Survival; Hematocrit; Histamine; Humans; Lung; Lung Transplantation; Platelet Glycoprotein GPIb-IX Complex; Platelet Glycoprotein GPIIb-IIIa Complex; Platelet Membrane Glycoproteins; Swine; Thrombin; Thromboxane B2; Transplantation, Heterologous

To investigate the effect of glucocorticoids on systemic inflammatory mediator release in rats with acute pancreatitis and the outcome of dexamethasone in treatment of acute pancreatitis.. Sixty-eight Wistar rats were divided into sham, acute pancreatitis, and treatment (intravenous dexamethasone 0.5 mg/kg) groups. Experimental acute pancreatitis was induced by the injection of 5% sodium taurocholate (0.1 ml/100 mg body weight) into the pancreatic-biliary duct. The blood samples were obtained and examined for 6-keto-PGI1alpha, TXB2 and IL-6 postoperatively at 3, 6 and 12 hours, respectively. The pancreatic samples were evaluated by a blinded method. Twelve-hour survival rate was determined and compared between the groups.. The high serum concentrations of 6-keto-PGI1alpha, TXB2 and IL-6 were noted in the rats with acute pancreatitis associated with pancreatic hemorrhage and necrosis. Their 12-hour survival rate was 42.9%. The rats in the treatment group survived with significantly reduced serum concentrations of 6-keto-PGI1alpha, TXB2 and IL-6 (P<0.05). Their pancreatic morphology was normal.. Dexamethasone may reduce the serum concentration of 6-keto-PGI1alpha, TXB2, and IL-6, and the severity of acute pancreatitis while increasing the survival rate of rats with acute pancreatitis.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Arachidonic Acid; Dexamethasone; Glucocorticoids; Inflammation Mediators; Interleukin-6; Male; Pancreatitis, Acute Necrotizing; Rats; Rats, Wistar; Survival Rate; Thromboxane B2

This work studied the effects of hydrocortisone treatment in experimental acute pancreatitis on cytokines, phospholipase A2, and breakdown products of arachidonic acid and survival. Edematous and necrotizing pancreatitis were induced in Wistar rats by cerulein hyperstimulation and retrograde intraductal infusion of sodium taurocholate, respectively. Hydrocortisone (10 mg/kg) was administered intravenously 10 minutes after induction of acute pancreatitis. Serum was assayed for phospholipase A2; interleukin (IL) 1beta, IL-6, IL-10, thromboxane B2; Prostaglandin E2; and leukotriene B4 at five different time points. A significant release of inflammatory mediators was seen only in the severe model. Hydrocortisone powerfully suppressed arachidonic acid breakdown products and only mildly attenuated the systemic increase of phospholipase A2 and pro- and antiinflammatory cytokines. The mortality rate after 72 hr in the severe model was 86%. Hydrocortisone treatment reduced mortality to 13% (P = 0.001; Fisher's exact test). Hydrocortisone seems to be effective in the treatment of the early systemic inflammatory response syndrome associated with severe acute pancreatitis.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Cytokines; Dinoprostone; Disease Models, Animal; Female; Hydrocortisone; Leukotriene B4; Pancreatitis; Rats; Rats, Wistar; Systemic Inflammatory Response Syndrome; 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

Topics: Acute Disease; beta-Thromboglobulin; Biomarkers; Blood Platelets; Humans; Myocardial Infarction; Osteonectin; Platelet Activation; Thromboxane B2

Models of brain injury in experimental animals have shown that the level of prostaglandins (PGs) is increased in damage brain tissue, and that PGs play an important role in secondary brain damage. Almost all previous studies of the relationship between PGs and brain injury have been carried out in animals. In the present study we show that the PGs change in humans with brain injury.. The plasma levels of thromboxane B2, 6-Keto-PGF2alpha, prostaglandin F2alpha, and prostaglandin E2 were measured by radioimmunoassay on the 1st, 3rd, 7th, and 14th days after brain injury. The same measurements were made on a control group of 26 healthy volunteers.. The levels of all four PGs were elevated, most markedly in the first week, with levels remaining high in the second week in the severely injured. On the first day levels were, on average, three times those found in the controls, with a seven-fold rise in some of the severely injured patients. Dividing the patients into three groups according to outcome, it was found that if the PGs were markedly increased to begin with and remained high, death or permanent disability was likely. In the group with good outcome, the levels dropped steadily from the initial high levels. The T/K ratio was studied. It related closely to the severity of injury, being higher in more severe injuries and decreasing with recovery. In patients who did not recover, the ratio increased steadily to its highest value on the 7th day, and remained high at the 14th.. Changes in PGs levels were closely related to the brain injury severity and its outcome, and there was a marked disturbance of the levels of PGs, which therefore appears to be an important indicator of secondary brain damage.

Topics: Acute Disease; Adolescent; Adult; Aged; Brain Injuries; Case-Control Studies; Child; Dinoprost; Dinoprostone; Female; Humans; Male; Middle Aged; Prostaglandins; Radioimmunoassay; Thromboxane B2; Time Factors

To determine the role of inflammatory products of phospholipid metabolism in acute otitis media (AOM), we infected 128 chinchillas with Streptococcus pneumoniae and randomly assigned them to one of four equal-sized treatment groups receiving intramuscular ampicillin sodium (control) or intramuscular ampicillin plus receptor blockers of platelet activating factor (WEB 2086, 5 mg/d orally), of leukotriene (MK 571, 0.5 mg/d orally), or of thromboxaneA2 (GR 32191B, 5 mg/d orally). All treatments were begun on day 2 postinoculation and continued for 10 days. On days 3, 6, 9, and 12, 8 animals from each group were sacrificed. Effusions were recovered for biochemical assay, and the right middle ears were prepared for histologic study. Differences among groups in the number of ears with effusion or in effusion volume were not statistically significant. In comparison to the control group, mucosal thickness and the number of ears with histopathologic signs of inflammation were significantly less in the GR and WEB treatment groups, but not the MK group. Also, effusion concentrations of free fatty acids, protease, and hydrolytic enzymes were significantly less in those groups. These results show that the addition of a receptor blocker for either platelet activating factor and/or thromboxane to ampicillin in the treatment of AOM reduces mucosal inflammation and decreases the production of other inflammatory chemicals. The failure of a receptor blocker of leukotrienes to moderate disease expression suggests either a less important role for these chemicals in AOM or an insufficient bioavailability of the specific MK 571 inhibitor. These results confirm that platelet activating factor and thromboxane are active mediators of inflammation in AOM.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Azepines; Biphenyl Compounds; Chinchilla; Dinoprostone; Ear, Middle; Fatty Acids, Nonesterified; Heptanoic Acids; Hydrolases; Leukotriene Antagonists; Leukotriene C4; Mucous Membrane; Otitis Media; Phospholipids; Platelet Activating Factor; Platelet Membrane Glycoproteins; Pneumococcal Infections; Propionates; Quinolines; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Receptors, Thromboxane; Thromboxane B2; Triazoles

Vascular smooth muscle cell (VSMC) proliferation and migration to the subintima or intimal hyperplasia (IH) occur after arterial injury and are thought to be induced by mitogenic factors released from activated platelets. Because low flow (LF) and shear have been attributed to the localization and progression of IH, we postulated that hemodynamic factors may regulate the degree of platelet activation, as measured by plasma thromboxane B2 (TXB2) and platelet-derived growth factor-AB (PDGF-AB) release at regions of experimental arterial injury.. The right common carotid artery (CCA) was subjected to balloon injury in 18 New Zealand White male rabbits. Flow in the injured CCA was reduced by out-flow ligation (LF group, n = 6) or increased by ligation of the left CCA (high flow [HF] group, n = 6). In six other animals, flow was preserved (normal flow [NF] group). Mean blood flow and pressure in the right CCA were measured thereafter at 10 and 30 minutes. Plasma TXB2 and PDGF-AB levels were determined with the enzyme-linked immunosorbent assay method in each animal with blood samples taken systematically before injury (baseline) and in the distal CCA at similar time points.. At 10 minutes, mean blood flow was reduced from 20 +/- 2 ml/min in the NF group to 7 +/- 1 ml/min in the LF group animals (p < 0.01) and increased to 32 +/- 2 ml/min in the HF group animals (p < 0.05). Mean arterial blood pressure did not differ among the groups. Hemodynamic parameters were similar at 10 and 30 minutes. TXB2 levels were more than fourfold greater in the LF group than in the HF and NF groups at both time points (p < 0.05). In addition, there was a twofold increase in plasma PDGF-AB level at 10 minutes in the LF group compared with baseline levels (p < 0.05).. Platelet activation at regions of acute vascular injury was determined to be flow dependent. Upregulated platelet activity in low flow conditions may be due to increased platelet exposure time to subendothelial collagen and is greatly attenuated if normal or increased flow is present.

Topics: Acute Disease; Animals; Blood Flow Velocity; Blood Platelets; Blood Pressure; Carotid Artery Injuries; Carotid Artery, Common; Catheterization; Cell Division; Cell Movement; Collagen; Disease Progression; Enzyme-Linked Immunosorbent Assay; Hemorheology; Hyperplasia; Male; Mitogens; Muscle, Smooth, Vascular; Platelet Activation; Platelet-Derived Growth Factor; Rabbits; Recombinant Proteins; Regional Blood Flow; Thromboxane B2; Time Factors; Tunica Intima; Up-Regulation

Various kinds of cells and their mediators are thought to be involved in the pathogenesis of bronchial asthma. However, changes in each mediator or relationship among mediators during an asthmatic attack have not been well documented. In this study, to clarify whether eosinophil protein X (EPX) is a marker which is distinct from leukotriene E4 (LTE4), or 11-dehydrothromboxane B2 (11DTXB2), we measured the urinary excretion of EPX, LTE4, and 11DTXB2 in 14 asthmatics who were admitted to the hospital with either an acute asthmatic attack or status asthmaticus. These patients included eight atopic and six non-atopic types of bronchial asthma, with a median age of 34.0 years. Urinary excretion of EPX was significantly high on admission with the asthmatic attack, and returned to control levels 175 [122 -384] microg/day when the patients were in the improved state (1036-317 microg/day, P < 0.01). Similar findings were observed in LTE4 (155-59 ng/day, P < 0.01) and 11DTXB2 (991-442ng/day, P<0.01). No significant differences in values were observed between atopic and non-atopic types of asthma in all three substances. When the individual data during the attack state were analysed, a significant correlation was observed between changes (%) in urinary EPX and those in urinary LTE4, but no such relationship was observed between changes (%) in urinary EPX and those in urinary 11DTXB2. These results suggest that measuring urinary EPX levels may be a useful marker for the understanding and management of the disease.

Topics: Acute Disease; Adolescent; Adult; Aged; Allergens; Asthma; Blood Proteins; Chromatography, High Pressure Liquid; Eosinophil-Derived Neurotoxin; Eosinophils; Female; Forced Expiratory Volume; Humans; Immunoglobulin E; Leukotriene E4; Male; Middle Aged; Ribonucleases; Thromboxane B2

Both platelet activation and lipid peroxidation are potential sources of vasoactive eicosanoids that can be produced via the cyclooxygenase pathway, ie, thromboxane (TX) A2, or by free radical-catalyzed peroxidation of arachidonic acid, ie, isoprostanes. We investigated the biosynthesis of TXA2 and F2-isoprostanes, as reflected by the urinary excretion of 11-dehydro-TXB2 and 8-epi-prostaglandin (PG) F2 alpha respectively, in 62 consecutive patients (30 men, 32 women; mean age, 67 +/- 14 years) with acute ischemic stroke.. At least two consecutive 6-hour urine samples were obtained during the first 72 hours after onset of symptoms. Urinary eicosanoids were measured by previously described radioimmunoassays.. Repeated periods of enhanced thromboxane biosynthesis were found in 52% of patients. Urinary 11-dehydro-TXB2 averaged 221 +/- 207 (mean +/- SD; n = 197; range, 13 to 967) pmol/mmol creatinine in 30 patients treated with cyclooxygenase inhibitors (mostly aspirin) at the time of study versus 392 +/- 392 (n = 186; range, 26 to 2533) in 32 untreated patients (P < .001). The corresponding values for 8-epi-PGF2 alpha excretion were 74 +/- 42 (range, 14 to 206) and 83 +/- 65 (range, 24 to 570) pmol/mmol creatinine (P > .05). The correlation between the two metabolites was moderate in both untreated patients (r = .41, P < .001) and patients with cyclooxygenase inhibitors (r = .31, P < .001). In a multiple regression analysis, increased thromboxane production was independently associated with severity of stroke on admission, atrial fibrillation, and treatment with cyclooxygenase-inhibiting drugs.. We conclude that during the first few days after an acute ischemic stroke (1) platelet activation occurs repeatedly in a cyclooxygenase-dependent fashion; (2) platelet activation is not associated with concurrent changes in isoprostane biosynthesis; (3) platelet activation is independently associated with stroke severity and atrial fibrillation; and (4) isoprostane biosynthesis is largely independent of platelet cyclooxygenase activity.

Topics: Acute Disease; Aged; Atrial Fibrillation; Brain Ischemia; Cerebrovascular Disorders; Cyclooxygenase Inhibitors; Dinoprost; Female; Humans; Lipid Peroxides; Male; Middle Aged; Platelet Activation; Reference Values; Thromboxane B2

Although several pathophysiological sequences, such as protease activation, free radical generation, and inflammatory mediator release, have been described in acute pancreatitis, the precise mechanism by which acute pancreatitis is initiated is unknown. Cellular calcium, a key physiological signaling element in cell function and also a crucial pathological intracellular messenger in cell injury, appears to be involved in the initiation and development of acute pancreatitis. The present study provides several lines of evidence supporting this suggestion. First, verapamil (a calcium channel blocker) administration was associated with a significant protection of rats from acute pancreatitis induced by high doses of cerulein (50 micrograms/kg/hr, subcutaneously), as evidenced both histologically and biochemically. Second, verapamil was found to minimize the increased tissue levels of calcium, platelet-activating factor, and thromboxane B2 detected during acute pancreatitis. Third, acute pancreatitis could be observed in rats with elevated serum calcium levels at low doses of cerulein (5 micrograms/kg/hr, subcutaneously), but could not be observed in rats with normal serum calcium levels treated with low doses of cerulein. It is proposed that cellular calcium, which is a critical signaling component in the synthesis and release of inflammatory mediators and several other events, may be an important factor in the pathogenesis of cerulein-induced acute pancreatitis.

Topics: Acute Disease; Animals; Calcium; Calcium Channel Blockers; Ceruletide; Drug Synergism; Male; Pancreas; Pancreatitis; Platelet Activating Factor; Rats; Rats, Sprague-Dawley; Thromboxane B2; Verapamil

This study examines the hypothesis that acute thermal injury decreases renal and splanchnic vasodilator eicosanoids. Anesthetized rabbits were subjected to sham or a 25% total body surface area burn and fluid resuscitated. At 2, 4, 6, 12, and 24 h postburn the superior mesenteric and renal arteries were cannulated and perfused in vitro with their end organs with Krebs buffer (pH 7.4, 37 degrees C). Renal and splanchnic prostaglandins (PGs) 6-keto-PGF1 alpha (PGI2), and PGE2, and thromboxane B2 (TxB2) release were measured by EIA at 15 min of perfusion. The major eicosanoids released were PGI2 from the splanchnic bed and PGI2 and PGE2 from the kidney. Renal PGE2 and PGI2 and splanchnic PGI2 release were decreased by 50% or more 12 h postburn (p < 0.01) but were restored to sham burn levels 24 h postburn. Loss of these endogenous renal and splanchnic vasodilators 12 h postburn may contribute to ischemia of both vascular beds at this critical time period following acute burn injury.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Burns; Dinoprostone; Epoprostenol; Kidney; Kinetics; Male; Prostaglandins; Rabbits; Splanchnic Circulation; Thromboxane B2

The effect of bradykinin on nitric oxide generation and eicosanoid production in the early stage of an experimental model of acute necrotizing pancreatitis induced by sodium taurocholate has been evaluated. We have compared the effect of administering a long-acting bradykinin antagonist, HOE 140, and an inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl esther L-NAME) on pancreatic prostanoid synthesis. Plasma lipase levels were increased after acute pancreatitis induction, and reduced after HOE 140 or L-NAME administration. Nitric oxide production and thromboxane B2 levels were increased after pancreatitis induction and the increases were reduced by L-NAME or HOE 140 administration. In contrast, increased prostacyclin production, reflected as 6-keto-PGF1 alpha levels, was not modified by L-NAME or HOE 140. Bradykinin seems to be involved in nitric oxide and thromboxane synthesis during the initial phases of acute necrohemorrhagic pancreatitis.

Topics: Acute Disease; Animals; Arginine; Bradykinin; Lipase; Male; Necrosis; NG-Nitroarginine Methyl Ester; Nitric Oxide; Pancreas; Pancreatitis; Rats; Rats, Wistar; Taurocholic Acid; Thromboxane B2

A comparative study in horses of the pharmacokinetics (PK) and pharmacodynamics (PD) of 2 extensively used nonsteroidal anti-inflammatory drugs (NSAIDs), flunixin (FXN) and ketoprofen (KTP), was carried out applying PK/PD modelling. To evaluate the anti-inflammatory properties of these drugs a model of acute inflammation, comprising surgically implanted subcutaneous tissue cages stimulated by intracaveal injection of carrageenan, was used. FXN elimination half-life (T1/2 beta) in plasma was 3.37 +/- 1.09 h. However, in exudate a much longer T1/2 beta was obtained (15.99 +/- 3.80 h). Apparent volume of distribution (Vdarea) for FXN was 0.317 +/- 0.126 l/kg and body clearance (ClB) was 0.058 +/- 0.004 l/kg/h. KTP displayed enantioselective pharmacokinetics, the S(+) enantiomer being predominant in plasma, exudate and transudate. T1/2 beta values for R(-) and S(+)KTP were, respectively, 1.09 +/- 0.19 h and 1.51 +/- 0.45 h (plasma) and 19.73 +/- 2.72 h and 22.64 +/- 4.34 h (exudate), respectively. R(-)KTP was cleared more rapidly than the S(+) enantiomer. ClB values were 0.277 +/- 0.035 l/kg/h and 0.202 +/- 0.022 l/kg/h, respectively. FXN and KTP pharmacodynamics was evaluated by determining their inhibitory effects on serum thromboxane (Tx)B2, exudate prostaglandin (PG)E2, leukotriene (LT)B4 and beta-glucuronidase (beta-glu) and intradermal bradykinin-induced swelling. Both drugs produced marked inhibition of serum TxB2 synthesis for up to 24 h, with no significant differences between the drugs. FXN was a more potent inhibitor of exudate PGE2, the EC50 for FXN being lower (P < 0.01) than that for KTP (0.019 +/- 0.010 microgram/ml and 0.057 +/- 0.009 microgram/ml, respectively). Neither drug had any effect on exudate LTB4 concentration. Differences between the 2 drugs were observed for the inhibition of beta-glu, the Emax for KTP being higher (P < 0.01) than for FXN. However, no differences were observed in other PD parameters. Both FXN and KTP inhibited bradykinin-induced swelling. Differences between the drugs were obtained for Emax, which was greater for FXN (P < 0.01) than for KTP. Equilibration half-life (T1/2Ke0) also differed, being much longer (P < 0.01) for FXN than for KTP. PK/PD modelling proved to be a useful and novel analytical technique for studying the pharmacodynamics of NSAIDs, with the advantage over classical in vitro methods that it provides data in the whole animal. By quantifying action-concentration interrelationships through PK-PD mod

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Clonixin; Cross-Over Studies; Dinoprostone; Exudates and Transudates; Glucuronidase; Half-Life; Horses; Inflammation; Ketoprofen; Leukotriene B4; Male; Models, Biological; Thromboxane B2

Endothelial injury in vivo induced by Rickettsia Conorii, the etiologic agent of Mediterranean Spotted Fever (MSF) has been recently demonstrated. We sought to determine whether platelet and/or coagulative activation in vivo can be demonstrated in the acute phase of MSF, through measurements of a major metabolite of thromboxane (TX) in the urine (11-dehydro-TXB2) and of plasma prothrombin fragment 1 + 2, whose levels reflect activation of prothrombin to thrombin. Moreover, we measured plasma endothelin-1 as marker of endothelial dysfunction. Our results provide biochemical evidence for the occurrence of TXA2-dependent platelet activation and thrombin generation in vivo, together with endothelial dysfunction. These phenomena could account for clinical manifestations of MSF, such as vasculitis and focal microthrombus formation. These results could also provide a rationale for testing the efficacy of aspirin or heparin in reducing the prothrombotic status of Rickettsiae diseases.

Topics: Acute Disease; Adult; Aged; Anticoagulants; Blood Coagulation Disorders; Boutonneuse Fever; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Peptide Fragments; Platelet Activation; Prothrombin; Rickettsia; Thromboxane B2; Vasculitis

Sixteen sheep were surgically prepared for chronic study. Seven days later, Escherichia coli endotoxin (10 ng/kg/min, lipopolysaccharide (LPS) group, n = 10) or an equivalent amount of 0.9% NaCl (Control group n = 6) was administered. Between 1 and 8 h post-LPS, there was a hypodynamic state with low cardiac index (CI, LPS 5.0 +/- 0.2; sham 6.3 +/- 0.4 liters/min/m2 at 4 h). During this period, the left ventricular end-systolic pressure-diameter relationship (ESPDR), a sensitive index of myocardial contractility, was also lower (LPS 10.4 +/- 1.2; sham 17.2 +/- 0.8 mmHg/mm). Mean pulmonary arterial pressure (PAP) and pulmonary vascular resistance index (PVRI) were remarkably increased 1 h after the administration of LPS (PAP:LPS 37.5 +/- 1.9; sham 21.8 +/- 0.9 mmHg, PVRI: LPS 600 +/- 58; sham 158 +/- 23 dynes x s x cm-5 x m2). The early changes in cardiopulmonary function occurred concomitantly with an elevation in tumor necrosis factor (LPS 1221 +/- 520; sham 0 +/- 0 pg/ml) and thromboxane B2 (LPS 1382 +/- 266; baseline 82 +/- 20 pg/ml) in arterial blood. Following this first phase, the sheep presented a persistent hyperdynamic state characterized by a significant increase in CI. The ESPDR continued to fall. By 24 h post-LPS the CI was 10.1 +/- 0.5 liters/min/m2 (sham, 6.3 +/- 0.3) but the ESPDR had fallen to 8.2 +/- 2.3 mmHg/mm (sham 16.0 +/- 3.0). The pulmonary hypertension was maintained for the duration of the LPS infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Animals; Blood Pressure; Cardiac Output; Endotoxins; Female; Heart Diseases; Lung; Lung Injury; Myocardial Contraction; Neutrophils; Pulmonary Circulation; Sheep; Thromboxane B2; Tumor Necrosis Factor-alpha; Vascular Resistance; Ventricular Function, Left

The role of nitric oxide in eicosanoid and oxygen-free radical production in the early stages of sodium taurocholate-induced acute necrotizing pancreatitis has been studied. Male Wistar rats were divided into three groups: group I: control group, a volume of 0.1 ml/100 g body wt saline solution was injected at low pressure in the pancreatic duct; group II: acute pancreatitis was induced by administration of 3.5% sodium taurocholate; and group III: intravenous administration of NG-nitro-L-arginine methyl esther (a nitric oxide synthase inhibitor) 5 min before induction of acute pancreatitis as stated for group II. At 5 and 60 min after induction of pancreatitis, blood and pancreas tissue samples were taken for assays. Increases in 6-keto PGF1 alpha, TXB2, PGE2, PGF2 alpha, and 12-HETE were observed in the pancreatic tissue. Lipoperoxidation was also enhanced and remained unaltered after nitric oxide inhibition. The fact that nitric oxide synthase inhibition could only reverse the increases in 6-keto PGF1 alpha and TXB2 levels indicates that in acute pancreatitis endothelial and platelet eicosanoid generation is mediated through an nitric oxide-dependent mechanism. In contrast, nitric oxide appears to be not related with oxygen free radical damage associated with acute pancreatitis.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Acute Disease; Animals; Arachidonic Acid; Arginine; Blood Platelets; Endothelium, Vascular; Hydroxyeicosatetraenoic Acids; Lipase; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Organ Size; Pancreas; Pancreatitis; Phospholipases A; Prostaglandins; Rats; Rats, Wistar; Reactive Oxygen Species; Taurocholic Acid; Thromboxane B2

The aim of this work is to establish a relationship between prostanoids and oxygen free radicals in the early stages of acute pancreatitis induced by sodium taurocholate and to study the possible cytoprotective effects of exogenous prostaglandin administration. Tissue prostanoid production (6-keto-prostaglandin F1 alpha, thromboxane B2, and prostaglandin E2) was studied after induction of an acute pancreatitis by intraductal administration of 3.5% sodium taurocholate (0.1 ml/100 mg). The effect of previous administrations of 16,16-dimethyl prostaglandin E2 (0.5 microgram/kg), indomethacin (20 mg/kg), or superoxide dismutase (13 mg/kg) was evaluated. Early pancreatitis induced significant increases of the three prostanoid levels as soon as 5 min after taurocholate administration. The administration of 16,16-dimethyl prostaglandin E2 was able to maintain the tissue prostanoid production at basal levels while superoxide dismutase treatment only partially prevented the increase of 6-keto-prostaglandin F1 alpha. On the other hand, indomethacin pretreatment, as expected, prevented the taurocholate-induced early prostanoid biosynthesis but increased the mortality, suggesting that endogenous prostanoids play a role in cellular defense mechanisms. The effect of superoxide dismutase suggests that oxygen free radicals are responsible, in part, for prostanoid enhanced biosynthesis in the earlier stages of necrohemorrhagic pancreatitis.

Topics: 16,16-Dimethylprostaglandin E2; 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Dinoprostone; Free Radicals; Indomethacin; Male; Pancreas; Pancreatitis; Prostaglandins; Rats; Rats, Wistar; Superoxide Dismutase; Taurocholic Acid; Thromboxane B2

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

The mechanisms leading to the hyperacute rejection of a vascularized xenograft are still incompletely understood. The first stage of the rejection process is when blood of the recipient comes into contact with the endothelium of the xenograft. A working heart model was used to examine endothelium-related processes and their impact on organ function. Pig hearts were perfused with porcine (autologous) or human (xenogeneic) blood. Cardiac function was evaluated by calculating the stroke work index, arteriovenous oxygen, coronary flow, and resistance. PgF1a as a marker of endothelial activation, its antagonist TXB2, and myoglobin reflecting myocardial damage were measured in the hemoperfusate. H&E and PAS staining and immunohistological demonstration of factor VIII-related antigen was performed. Xenogeneic perfused porcine hearts showed significantly less stroke work, a higher arteriovenous oxygen difference, and an increased coronary resistance. Factor VIII-related antigen could not be demonstrated immunohistologically on the endothelium after xenogeneic perfusion. PgF1a levels were significantly higher in the xenogeneic hemoperfusate, indicating endothelial cell activation. The concentration of myoglobin in the hemoperfusate remained within normal values and was similar during autologous and xenogeneic perfusion. Therefore endothelium-related processes are likely to affect the coronary circulation--thus being one mechanism leading to diminished cardiac performance during hyperacute rejection.

Topics: Acute Disease; Animals; Blood; Endothelium, Vascular; Factor VIII; Female; Graft Rejection; Heart Function Tests; Heart Transplantation; Humans; Male; Myoglobin; Perfusion; Prostaglandins F; Swine; Thromboxane B2; Transplantation, Heterologous

Systemic prostacyclin and thromboxane A2 production in rat experimental acute pancreatitis has been evaluated by measuring the urinary excretion of the 2,3-dinor 6-keto prostaglandin F1 alpha and 2,3-dinor thromboxane B2, respectively. Acute pancreatitis was induced by intraductal administration of 4.5% sodium taurocholate (0.1 ml/100 mg body weight) and intravenous cerulein perfusion (5 micrograms/kg/hr) for 6 hr, respectively. Urinary excretion of 2,3-dinor 6-keto prostaglandin F1 alpha and 2,3-dinor thromboxane B2 were much more important in sodium taurocholate- than in cerulein-induced acute pancreatitis. These data confirm an altered prostacyclin and thromboxane metabolism occurring in experimental acute pancreatitis. Phospholipase A2 activity and the effect of gabexate mesilate on the arachidonate metabolism were also evaluated.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Amylases; Animals; Ceruletide; Epoprostenol; Gabexate; Lipase; Male; Pancreatitis; Phospholipases A; Phospholipases A2; Rats; Rats, Sprague-Dawley; Taurocholic Acid; Thromboxane A2; Thromboxane B2

The principal causes of failure of a pancreas transplant are rejection and vascular thrombosis. There is an unusually high attrition rate for pancreas transplants, but study models have been difficult to develop. In a rat model that allows study of acute rejection to the exclusion of nonspecific effects of transplant surgery on the pancreas, in vitro synthesis of prostacyclin (PGI2) and thromboxane A2 (TXA2) by transplanted pancreas and the blood vessels transplanted with it was measured using an RIA for their stable hydrolysis products 6-keto-prostaglandin F1 alpha and thromboxane B2 (TXB2). TXB2 synthesis was significantly greater in allotransplanted pancreas than isotransplanted pancreas from the 5th day after transplantation. Rejection was complete in the allografted group 7-9 days after transplantation. 6-Keto-prostaglandin F1 alpha synthesis was similar in the pancreas for both allografts and isografts. Similar changes were seen in aorta, celiac artery, superior mesenteric artery, and portal vein transplanted with the pancreas. In the transplanted aorta, TXB2 was significantly greater in the allograft group from the third posttransplant day. A group of CsA-treated allografts sampled after 9 days had transplanted pancreatic parenchymal and vascular prostanoid synthesis in the isograft range. The changes in PGI2 and TXA2 synthesis that accompany cellular rejection may mediate vascular failure in rejecting pancreas transplants, and changes in PGI2 and TXA2 synthesis in blood vessels transplanted with the pancreas could promote early vascular thrombosis.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Aorta; Celiac Artery; Cyclosporine; Epoprostenol; Graft Rejection; Male; Mesenteric Artery, Superior; Pancreas; Pancreas Transplantation; Rats; Rats, Inbred Strains; Thrombosis; Thromboxane A2; Thromboxane B2; Transplantation, Homologous; Transplantation, Isogeneic; Vena Cava, Inferior

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

Several studies have reported that prostanoids are involved in many of the physiopathological mechanisms underlying acute pancreatitis but their precise role in this disease remains to be established. The objective of this work is to evaluate the variation of local tissue production of prostanoids and lipoxygenase metabolites of arachidonic acid in acute pancreas inflammation induced by intraductal administration of 3.5% sodium taurocholate (0.1 ml/100 mg body weight) in rats. Pancreatic tissue levels of leukotriene B4 (LTB4), 15 hydroxyeicosatetraenoic acid (15-HETE), 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were determined by HPLC-RIA techniques at 5 and 60 minutes after induction of acute pancreatitis (AP). Prostanoids increased significantly at 5 minutes and LTB4 and 15-HETE at 60 minutes. These data confirm that the prostanoid imbalance could be considered as an early specific response of the pancreas to the inflammatory events characteristic of induced AP while the altered levels of the lipoxygenase products (LTB4 and 15-HETE) would be more of a nonspecific organ response associated to the high cellular infiltration rate and necrosis observed in the late phases of acute pancreatitis.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Dinoprostone; Hemorrhage; Hydroxyeicosatetraenoic Acids; Kinetics; Leukotriene B4; Lipoxygenase; Male; Pancreas; Pancreatitis; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Taurocholic Acid; Thromboxane B2

Vasoconstriction during acute renal allograft rejection may be regulated by increased formation of vasoactive prostanoids. To address this hypothesis we investigated the biosynthesis of thromboxane (Tx)A2, a potent vasoconstrictor and platelet agonist, of prostacyclin (PGI2), a vasodilator and platelet antagonist, and of prostaglandin (PG)E2, a mediator of salt and water excretion, in nine children with 12 acute rejection episodes, prospectively during the first 7 weeks after renal transplantation. We used physicochemical analysis of stable urinary prostanoid index metabolites. Rejection crises were associated with an increase in TxB2 excretion from baseline median 9.2 (range 1.9-18.6) ng/h/1.73 m2 to 21.2 (range 10.0-133.0) ng/h/1.73 m2 (P < 0.005) during acute rejection episodes. Methylprednisolone pulse therapy resulted in a partial reduction, but not normalization of TxB2 excretion. Urinary 2,3-dinor-TxB2 was slightly stimulated during allograft rejection, urinary 11-dehydro-TxB2 did not change significantly. Renal PGI2 and PGE2 biosynthesis remained essentially unchanged. In contrast to acute graft rejection, patients with chronic graft rejection and those with stable graft function on different immunosuppressive regimens with or without cyclosporin A did not present stimulated renal TxA2 formation. Increased renal TxA2 formation in acute renal allograft rejection is likely to mediate vasoconstriction and potentiate the loss of renal blood flow and glomerular filtration rate, in the absence of an adequate response of the renoprotective prostanoids PGI2 and PGE2.

Topics: Acute Disease; Adolescent; Child; Child, Preschool; Creatinine; Cyclosporine; Female; Graft Rejection; Humans; Kidney Transplantation; Male; Middle Aged; Prostaglandins; Thromboxane A2; Thromboxane B2; Transplantation, Homologous

Clinical and experimental studies suggest that platelets have a major role in the pathogenesis of cerebral ischemia. However, ex vivo both platelet aggregation studies and measurements of platelet-derived products in patients with cerebral ischemia have shown inconsistent results. The present study was designed to resolve this inconsistency.. We have measured the urinary excretion of a thromboxane metabolite, 11-dehydro-thromboxane B2, by a previously validated radioimmunoassay technique in 51 patients with acute cerebral ischemia who had experienced either a transient ischemic attack (14 patients) or an ischemic stroke (37 patients) and in 20 control patients with nonvascular neurological disorders. The median time between the onset of symptoms and urine sampling was 24 hours (range, from 2 hours to 8 days).. The excretion rate of immunoreactive 11-dehydro-thromboxane B2 ranged between 39 and 478 pmol/mmol creatinine in patients with a transient ischemic attack and between 23 and 5,916 pmol/mmol creatinine in stroke patients, with 29% (p = 0.18) and 51% (p = 0.004) of the urine samples, respectively, exceeding the upper limit of the control samples (251 pmol/mmol creatinine [mean +/- 2 SD]) (p = 0.01). In stroke patients, metabolite excretion was not related to the type (cortical or "lacunar") or site of cerebral infarction. Low-dose aspirin (50 mg per day for 7 days) reduced the urinary excretion by approximately 85% in 11 consecutive stroke patients.. We conclude that 1) episodes of enhanced thromboxane biosynthesis are detected infrequently in patients with a transient ischemic attack, 2) aspirin-suppressible episodes of increased thromboxane formation can be detected during the early phase of acute ischemic stroke, and 3) this finding may provide a rationale for testing the efficacy and safety of this drug in this setting.

Topics: Acute Disease; Aged; Aged, 80 and over; Blood Platelets; Brain Ischemia; Cerebrovascular Disorders; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Prospective Studies; Thromboxane B2

The effects of a long-acting somatostatin analog (SMS 201-995) were studied in an established model of acute necrotizing pancreatitis in rats. SMS 201-995, when given prior to induction of pancreatitis, decreased the mortality rate from 100% to 40% (P = 0.0001). When treatment was given after induction of pancreatitis, the mortality rate was 75% (P = 0.2). Administration of SMS 201-995 did not influence the serum concentrations of amylase markedly, but the lipase levels were significantly lowered (P less than 0.05). The low levels of serum insulin and the glucose level in whole blood were not influenced. The volume of ascitic fluid was reduced (P less than 0.01). Moreover, less peritoneal fat necrosis was seen, suggesting a reduction in toxic factors in the ascitic fluid. Treatment with SMS 201-995 prior to induction of pancreatitis caused a significant increase in the levels of circulating 6-keto-PGF1 alpha, the stable metabolite of prostaglandin I2 (P less than 0.01). The levels of thromboxane B2 and prostaglandin E2 did not change significantly. The present data support the hypothesis that SMS 201-995 is an activator of prostaglandin I2, thereby modifying the course of the disease.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Amylases; Animals; Dinoprostone; Eicosanoids; Lipase; Male; Necrosis; Octreotide; Pancreas; Pancreatitis; Rats; Rats, Inbred Strains; Thromboxane B2

We tested the preventive effects of catalase, an enzymatic scavenger of hydrogen peroxide, or dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, on intravenous alloxan-induced lung edema in four groups of pentobarbital sodium-anesthetized, ventilated dogs for 3 h: saline (20 ml.kg-1.h-1) infusion alone (n = 5), alloxan (75 mg/kg) + saline infusion (n = 5), catalase (150,000 U/kg) + alloxan + saline infusion (n = 5), or DMSO (4 mg/kg) + alloxan + saline infusion (n = 5). Catalase or DMSO significantly prevented the increase in plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha over 3 h after alloxan and the accumulation of extravascular lung water after 3 h [3.95 +/- 0.52 (SE) g/g with catalase, 3.06 +/- 0.42 g/g with DMSO] but not early pulmonary arterial pressor response. An electron microscopic study indicated that catalase or DMSO significantly reduced the endothelial cellular damages after alloxan. These findings strongly suggest that hydrogen peroxide and hydroxyl radical are major mediators responsible for intravenous alloxan-induced edematous lung injury in anesthetized ventilated dogs.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Alloxan; Animals; Blood Pressure; Catalase; Dimethyl Sulfoxide; Dogs; Endothelium; Free Radical Scavengers; Free Radicals; Leukocyte Count; Microscopy, Electron; Platelet Count; Pulmonary Alveoli; Pulmonary Circulation; Pulmonary Edema; Pulmonary Wedge Pressure; Thromboxane B2

The aim of this study was to investigate the effect of Nafamostat mesilate (FUT-175) on some blood platelet properties during the first hours of acute experimental pancreatitis (AEP) in dogs. A significant decrease in platelet count, hyperaggregability of platelets by ADP and PAF as well as an increased level of TXB2, were found in the early stage of AEP. No changes in platelet aggregation induced with AA were demonstrated. FUT-175 prevented a decrease in platelet number and inhibited platelet aggregation induced with ADP, PAF and AA when it was given immediately after induction of AEP. No evident changes in TXB2 levels in dogs treated with FUT-175 were found. Our results indicate that the positive effect of FUT-175 in AEP in part depends on its antiaggregatory action.

Topics: Acute Disease; Animals; Benzamidines; Blood Platelets; Dogs; Guanidines; Male; Pancreatitis; Platelet Aggregation Inhibitors; Platelet Count; Protease Inhibitors; Thromboxane B2

We analyzed edema fluid in two cases of reexpansion pulmonary edema during thoracotomy. High value of the fluid to plasma protein concentration ratio indicates an increase in pulmonary microvascular permeability. There were marked increases in polymorphonuclear leukocyte (PMN) count and concentration of PMN-elastase in edema fluid. There were also increases in concentrations of thromboxane B2 and 6-keto-PGF1-alpha in both edema fluid and plasma. These findings strongly suggest that the mechanism of reexpansion pulmonary edema is an inflammatory response and that PMNs in the reexpanded lung may play a role in the increase in permeability.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adolescent; Adult; Exudates and Transudates; Female; Humans; Inflammation; Pancreatic Elastase; Proteins; Pulmonary Atelectasis; Pulmonary Edema; Thromboxane B2

We studied the effects of the calcium channel blocker, verapamil on experimental acute pancreatitis (AP) in rats. The pancreatic blood flow (PBF) and pancreatic tissue perfusion (PTP) were measured after induction of AP. At the same time, the plasma levels of TXB2 and 6-keto-PGF1 alpha were determined by radioimmunoassay. The survival rate and the mean survival time after induction of AP were determined and the pancreatic histology was examined by light and electron microscopy. The results demonstrated a significant early fall in PBF and PTP, a marked increase in TXB2 levels and a slight increase in 6-keto-PGF1 alpha after induction of AP. Treatment with 0.1 mg/100 g verapamil significantly increased PBF and PTP, and decreased TXB2, resulting in a normalization of TXB2/6-keto-PGF1 alpha ratio. The treated animals also exhibited significant increase in the survival rate and the survival time. They also showed decrease in the severity of pancreatic hemorrhage and necrosis, and in the damage to the cellular ultrastructures. These data suggest that calcium blockade increases PBF and PTP, limits the prostanoid imbalance in the early phase of AP, and may influence the development of experimental acute pancreatitis in rats.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Female; Male; Pancreas; Pancreatitis; Rats; Rats, Inbred Strains; Regional Blood Flow; Thromboxane B2; Verapamil

We have compared the early development (0-4h) of two acute non-specific inflammatory reactions induced by the intrapleural injection of isologous serum or a suspension of CaPP crystals. The intensity of the reactions was assessed in terms of the exudate volume, the number and ratio of pleural cells and different cell functions and secretions. The number of exudative cells elicited by isologous serum was higher than with CaPP but the PMN/Monocytes ratio was the same. The amount of protein in the serum-induced exudate was constant from 1 h to 4 h and was similar in the CaPP-induced pleural exudate at the latter time. The amount of complement increased similarly in the two models. The chemotactic potency of the exudates and cell supernatants following incubation showed similar values in the two models. Eicosanoid levels were higher in CaPP--than in isologous serum-induced exudates. Prostacyclin and peptidoleukotrienes were released in specially large amounts at the very outset of the inflammatory reactions.

Topics: Acute Disease; Animals; Calcium Phosphates; Cells, Cultured; Eicosanoids; Epoprostenol; Leukocytes, Mononuclear; Leukotriene B4; Male; N-Formylmethionine Leucyl-Phenylalanine; Pleurisy; Rats; Rats, Inbred Strains; SRS-A; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Azepines; Female; Graft Rejection; Hemoperfusion; Humans; Kidney Transplantation; Male; Platelet Activating Factor; Swine; Thromboxane B2; Transplantation, Heterologous; Triazoles

The administration of the aminonucleoside of puromycin (PAN) to rats causes the nephrotic syndrome that is associated with an acute decline in renal function, and an interstitial infiltrate. We examined whether essential fatty acid deficiency (EFAD), which inhibits macrophage infiltration in glomerulonephritis, affects PAN-induced renal dysfunction. Both control and EFAD rats developed proteinuria that resolved over 28 d. After PAN administration, there was a prominent infiltration of macrophages in rats fed a normal diet. The infiltrate was prevented by the EFAD diet. The absence of a macrophage interstitial infiltrate was associated with a significantly higher Cin in the EFAD rats than in controls at 7 d (5.21 +/- 1.19 versus 0.39 +/- 0.08, P less than 0.002 ml/min/kg BW). In addition, CPAH fell to less than 10 ml/min/kg BW by day 7 in controls, but remained the same as normal in the EFAD. After administration of PAN to control rats, there was no increase in urinary thromboxane excretion or an increase in glomerular thromboxane production. Furthermore, the effect of EFAD could not be mimicked by the administration of a thromboxane synthase inhibitor. Irradiation-induced leukopenia in rats on a normal diet markedly improved glomerular filtration and renal blood flow in acutely nephrotic rats. EFAD prevents the interstitial cellular infiltrate and the renal ischemia associated with experimental nephrosis. The recruitment of mononuclear cells into the kidney following PAN directly contributes to the decline in renal function.

Topics: Acute Disease; Animals; Fatty Acids, Essential; Female; Kidney; Kidney Diseases; Leukopenia; Macrophages; Methacrylates; Nephrotic Syndrome; Puromycin Aminonucleoside; Rats; Rats, Inbred Lew; Thromboxane B2

The changes of the plasma thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, the stable metabolites of TXA2 and PGI2, respectively and their effects on platelet counts, platelet aggregation and hypotension were studied in patients with AOSC. The results showed that the plasma TXB2, 6-keto-PGF1 alpha and 6-keto-PGF1 alpha/TXB2 ratios in these patients were markedly increased, however, the platelet counts markedly decreased and platelet aggregation inhibited significantly. After operation, they recovered to normal gradually. There were negative correlation between TXB2 with platelet count and 6-keto-PGF1 alpha with platelet aggregation, as well as both TXB2 and 6-keto-PGF1 alpha with blood pressure. TXA2 was an important factor which lead to platelet decrement and take part in the pathological course of disseminated intravascular coagulation (DIC) and multiple organ failure (MOF), but PGI2 might play an important role in improving microcirculation and preventing DIC and MOF through the inhibition of platelet aggregation.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adult; Cholangitis; Cholelithiasis; Female; Humans; Male; Platelet Aggregation; Platelet Count; Thromboxane B2

The role of blood platelets in the disturbed haemostasis in acute pancreatitis is not fully elucidated. The aim of this study was to evaluate the blood platelet function during the first hours of acute experimental pancreatitis (AEP) in dogs. AEP was induced by the retrograde injection of bile and trypsin into the main pancreatic duct. Platelet count, platelet aggregation induced with ADP, PAF, AA as well as plasma Beta-TG and TXB2 levels were determined. At 30 min after induction of AEP a significant decrease of platelet count was noted; these changes were observed until 4 th hr. At 30 min as well as at 60 min of AEP increased sensitivity of platelet aggregation to ADP was found. After that time evident decrease of platelet aggregation to ADP was shown. Platelets sensitivity to PAF was higher at 30 min of AEP whereas 60 min, 2 and 4 hrs after AEP normalization of platelet aggregation by PAF was observed. The significant increase of plasma Beta-TG and TXB2 concentrations corresponded well to changes of platelet aggregation. These results indicate that AEP affects blood platelet function with the drop of their count.

Topics: Acute Disease; Adenosine Diphosphate; Animals; Arachidonic Acid; Arachidonic Acids; beta-Thromboglobulin; Blood Platelets; Dogs; Hemostasis; In Vitro Techniques; Pancreatitis; Platelet Activating Factor; Platelet Aggregation; Platelet Count; 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

Infused into sheep, paraquat causes increased flow of protein-rich lung lymph, increased prostanoid production, and neutrophil accumulation in the lung. The effects of high-dose methylprednisolone on the response to paraquat infusion were studied in awake sheep with chronic lung lymph fistulas. Seven sheep were infused with paraquat (30 mg/kg) alone. Six sheep received methylprednisolone (1.0 g plus 0.5 g/h intravenously), beginning 30 min before paraquat (pretreatment), and 5 received methylprednisolone, beginning 4 h after paraquat (post-treatment). Neutrophil accumulation in the lung was measured in biopsy tissue taken at baseline and at postmortem. Methylprednisolone pretreatment significantly prevented the increase in lung lymph flow (paraquat, from 4.4 +/- 0.3 to 11.1 +/- 0.8 ml/h, p less than 0.05; pretreatment, from 4.8 +/- 0.9 to 3.7 +/- 0.3, NS), and the increase in lymph-to-plasma protein concentration ratio (paraquat, from 0.69 +/- 0.02 to 0.80 +/- 0.02, p less than 0.05; pretreatment, from 0.66 +/- 0.06 to 0.60 +/- 0.02, NS) during 8 h after paraquat infusion. Treatment with methylprednisolone after paraquat also reduced the changes in lung lymph flow and protein clearance. Methylprednisolone prior to paraquat significantly inhibited accumulation of 6-keto-PGF1 alpha in lymph and plasma, but did not significantly inhibit accumulation of TxB2 in lymph or plasma. The number of neutrophils in the paraquat lungs was 3 to 4 times that in the control lungs, with or without methylprednisolone. Methylprednisolone pretreatment prolonged the survival time, but did not prevent death within 48 h after paraquat infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Carbon Dioxide; Hemodynamics; Leukocyte Count; Lung; Lymph; Methylprednisolone; Oxygen; Paraquat; Proteins; Sheep; Thromboxane B2

To establish whether or not urinary excretion TxB2 is a useful parameter in the diagnosis of acute renal rejection, 45 renal transplant patients were studied and classified in four groups: Group A. Ten observations of satisfactory clinical outcome (without either acute rejection or tubular necrosis). Urinary TxB2 was initially increased but had settled to normal by the 3rd postoperative day. Two patients had subsequent increases. Group B. Twenty-five episodes of acute rejection on a previously satisfactorily functioning graft. Nineteen had increases in TxB2 values before serum creatinine increased. Group C. Five episodes of tubular necrosis without acute rejection. The evolution was similar to Group A. Group D. Nine acute episodes of rejection on kidneys with tubular necrosis. The urinary output of TxB2 was increased from the beginning. This increase was maintained until the rejection was treated. This group had the highest values of urine TxB2. The principal significance of this parameter lies in its precocity and in its utility for diagnosis of acute rejection in the graft with tubular necrosis, as the persistence of raised values of TxB2 in the urine beyond the 3rd postoperative day is highly suggestive of an acute rejection.

Topics: Acute Disease; Adolescent; Adult; Graft Rejection; Humans; Kidney Transplantation; Kidney Tubular Necrosis, Acute; Middle Aged; Thromboxane B2

In an investigation of the pathogenesis of acute necrotizing pancreatitis (ANP) the plasma levels of TXB2, 6-keto-PGF1 alpha, and PGE2 were measured in rats. After induction of ANP by injection of 5% sodium taurocholate into the pancreatic duct, a marked increase in TXB2 levels and a slight increase in 6-keto-PGF 1 alpha levels were found. PGE2 levels decreased. Mortality was 100% within 30 h. Pretreatment with chloroquine, a phospholipase A2 inhibitor, led to a inhibition of TXB2 production, whereas 6-keto-PGF1 alpha and PGE2 levels showed a surprising slight elevation in the first 6 h. Pretreatment with chloroquine decreased mortality by 30%. Pretreatment with FPL 55712, a leukotriene synthesis blocker, caused an increase in TXB2 and PGE2 levels, whereas the formation of 6-keto-PGF1 alpha remained unaltered. Two out of nine animals survived after pretreatment with FPL 55712. The results of the present study indicate that arachidonate end products are involved in ANP. The significance of the high TXB2 levels, decreased PGE2 levels, and only slightly elevated 6-keto-PGF1 alpha levels during ANP requires further investigation. The thromboxane A2 to prostacyclin ratio may be important.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Chloroquine; Chromones; Dinoprostone; Male; Necrosis; Pancreatitis; Prostaglandins; Prostaglandins E; Rats; Rats, Inbred Strains; Thromboxane B2

We sought to determine the effect of corticosteroid therapy in a new acute model of oxidant lung injury, thoracic irradiation in awake sheep. Sheep were irradiated with 1,500 rads to the whole chest except for blocking the heart and adjacent ventral lung. Seven experimental sheep were given methylprednisolone (1 g intravenously every 6 h for four doses) and thoracic irradiation; control sheep received only irradiation. In irradiated control sheep, lung lymph flow increased from baseline (7.6 ml/h) to peak at 3 h (13.2), and lung lymph protein clearance increased from 5.1 to 9.7 ml/h. Mean pulmonary artery pressure increased in the irradiated control sheep from 19 to 32.4 cm H2O, whereas the lung lymph thromboxane concentration increased from 0.09 to 6.51 ng/ml at 3 h. Arterial oxygen tension in irradiated control sheep fell gradually from 86 mm Hg at baseline to 65 mm Hg at 8 h. Methylprednisolone administration significantly prevented the increase in lung lymph protein clearance, mean pulmonary artery pressure, and lung lymph thromboxane concentration. Methylprednisolone also prevented the fall in arterial oxygen tension after thoracic irradiation, but did not prevent a further decrease in lymphocytes in blood or lung lymph after radiation. We conclude that corticosteroid therapy prevents most of the acute physiologic changes caused by thoracic irradiation in awake sheep.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Blood Cell Count; Blood Gas Analysis; Hemodynamics; Leukocyte Count; Lung; Lung Diseases; Lymph; Methylprednisolone; Proteins; Pulmonary Artery; Radiation Injuries, Experimental; Sheep; Thorax; Thromboxane B2

Kidneys from rats subjected to bilateral ureteral obstruction (BUO), unilateral ureteral obstruction (UUO) and UUO with subsequent release were analyzed for leukocyte infiltration. A time-dependent influx of leukocytes, predominantly macrophages and suppressor T lymphocytes, occurred in both the cortex and medulla following obstruction, and disappeared with release of the obstruction. Glomerular macrophages declined following obstruction but increased to levels above control following release. The influx of leukocytes following obstruction was paralleled by an increase in thromboxane B2 excretion by the kidney and coincided with a decrease in glomerular filtration rate (GFR). This would suggest that an influx of immune cells is a prominent feature of the acute renal response to ureteral obstruction. These cells may modulate some of the post-obstructive alterations in renal function via the production of vasoactive substances, such as thromboxane A2.

Topics: Acute Disease; Animals; Kidney; Leukocytes; Macrophages; Rats; Rats, Inbred Strains; T-Lymphocytes; Thromboxane B2; Ureteral Obstruction

The possible role of thromboxane A2 (TXA2) in acute necrotizing pancreatitis (ANP) was investigated in rats. After ANP was induced by injecting sodium taurocholate (5% w/v) into the pancreatic duct, the thromboxane B2 (TXB2) levels in plasma increased significantly. The effects of indomethacin, a general blocker of prostaglandin synthesis, on survival time and on plasma TXB2 levels were compared with those of dazoxiben, a more specific blocker of TXA2 synthesis, and Flunarizine, a calcium entry blocker known to inhibit the effects of TXA2. In a test group without any treatment, all animals died within 30 h of ANP induction. Although TXB2 levels were lowered by the administration of indomethacin, dazoxiben, and Flunarizine, survival times were not significantly altered. Indomethacin pretreatment had no beneficial effect, whereas 30% and 40% of the animals survived for 36 h after treatment with Flunarizine and dazoxiben, respectively. The results of the present study indicate that inhibition of TXA2 synthesis alone does not dramatically alter survival time. However, a potential role for other arachidonate metabolites in ANP cannot be ruled out by this study.

Topics: Acute Disease; Animals; Flunarizine; Imidazoles; Indomethacin; Male; Necrosis; Pancreatitis; Rats; Rats, Inbred Strains; Thromboxane A2; Thromboxane B2

To assess the role of platelets in thrombohemorrhagic complications of acute respiratory failure (ARF), we studied platelet function in 13 ARF patients admitted for intensive care, in six acutely ill intensive care patients without evidence of acute lung injury (non-ARF), and in 10 normal subjects. Platelet counts in ARF and non-ARF patients were similar to the normal range. The bleeding time of the ARF patients (8.5 +/- 0.9 min) was significantly longer (p less than 0.01) than the normal (4.8 +/- 0.2 min) but similar to non-ARF patients (5.4 +/- 0.8 min). The bleeding time prolongations in ARF patients were unrelated to platelet concentration. Platelet aggregation induced by ADP and thrombin was normal in both ARF and non-ARF patient groups. The epinephrine response was impaired in one non-ARF patient and in three ARF patients; collagen-induced aggregation was absent in two ARF patients, with a prolonged bleeding time. Levels of VIII:C and vWF in both groups of patients were similar to the normal level, but VIIIR:Ag levels in ARF patients (407 +/- 45% of normal) were higher (p less than 0.01) than in both non-ARF patients (210% +/- 10%) and normal subjects (106% +/- 4). The electrophoretic mobility of VIIIR:Ag was abnormal in ARF patients. The prolonged bleeding time in ARF patients appears to result from the qualitative and quantitative VIIIR:Ag defect. beta-Thromboglobulin levels were greater (p less than 0.01) in ARF patients (87.6 +/- 6.9 ng/ml; p less than 0.001) than in non-ARF patients (46.2 +/- 3.1 ng/ml) or in normal subjects (25.3 +/- 2.5 ng/ml p less than 0.0001). However, platelet factor 4 plasma levels in ARF patients (18 +/- 1.6 ng/ml) did not differ from those in non-ARF patients (15.0 +/- 3.0 ng/ml), but both were significantly different from normal (6.1 +/- 0.8 ng/ml). Plasma thromboxane B2 (T X B2) levels were not different from normal values in either ARF or non-ARF patients, but 6-keto-PGF1 alpha levels were significantly reduced (p less than 0.01) in ARF patients (215 +/- 43 pg/ml) compared to normal values (381 +/- 34 pg/ml). Non-ARF patients had 6-keto-PGF1 alpha levels (285 +/- 111 pg/ml) midway between the normal values and those of ARF patients. Our results suggest that in vivo platelet activation occurs in ARF. ARF patients have quantitative and qualitative platelet defects that may contribute to thrombotic and hemorrhagic complications.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antigens; beta-Thromboglobulin; Bleeding Time; Blood Platelets; Factor VIII; Female; Humans; Lung; Male; Middle Aged; Platelet Aggregation; Platelet Count; Platelet Factor 4; Respiratory Insufficiency; Thromboxane B2; von Willebrand Factor

Arterial plasma concentrations of thromboxane B2 (TxB2), prostaglandin F2 alpha (PGF2 alpha) and 6-keto-prostaglandin F1 alpha (PGF1 alpha) were measured during endotoxin-induced acute respiratory failure (ARF) in anesthetized 10-12 wk old pigs. A 4.5 hour (hr) infusion of endotoxin resulted in a biphasic pattern of ARF. Phase 1 (0-2 hr) was characterized by increased pulmonary artery pressure, pulmonary vascular resistance (PVR), and alveolar-arterial O2 gradient (delta A-aO2), and decreased cardiac index (CI) and lung dynamic compliance (LDC). Following a return of PVR and CI values towards baseline, a second phase (2-4.5 hr) of deteriorating function occurred and was characterized by additional increases in PVR and delta A-aO2 and decreases in CI and LDC. Baseline (i.e., 0 hr) plasma TxB2 concentrations were 241 +/- 24 pg/ml; these values peaked at 0.5 hr (3228 +/- 712 pg/ml) and declined to 1635 +/- 453 pg/ml at 4.5 hr. Plasma concentrations of PGF2 alpha slowly increased from a baseline value of 154 +/- 32 pg/ml to 2355 +/- 738 pg/ml at 4.5 hr, while PGF1 alpha values increased from 54 +/- 2 pg/ml at 0 hr to 503 +/- 172 pg/ml at 4.5 hr. Time-matched control pigs showed no changes in pulmonary hemodynamics or in plasma TxB2, PGF2 alpha or PGF1 alpha levels. These results indicate that cyclooxygenase products are increased during both phases of endotoxin-induced ARF in pigs.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Arteries; Dinoprost; Endotoxins; Escherichia coli; Hemodynamics; Lung; Prostaglandins F; Respiratory Insufficiency; Swine; Thromboxane B2

The development of reproducible models of acute inflammation in which inflammatory heat is easily quantified and from which inflammatory exudate is readily harvested has facilitated studies in the horse of the actions of steroids and non-steroidal anti-inflammatory drugs (NSAIDS). Blockade of the synthesis of eicosanoids and suppression of inflammatory heat by clinical dose rates of NSAIDS suggests a causal link between the two events and provides further evidence for a role of these compounds in acute equine inflammation. The tendency for enolic and carboxylic acids NSAIDS to accumulate in inflammatory exudate may account for the duration of action of these compounds in inhibiting exudate eicosanoid synthesis and the data confirm clinical experiences with these drugs. A novel NSAID which inhibits both cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism, BW540C, and two anti-inflammatory steroids, betamethasone and dexamethasone, have been evaluated in the models of equine inflammation with some interesting and unexpected findings. This paper emphasises the interrelationships between the inflammatory process and the actions and fate of anti-inflammatory drugs.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Chemical Phenomena; Chemistry; Dinoprostone; Disease Models, Animal; Epoprostenol; Horse Diseases; Horses; Inflammation; Prostaglandins E; Steroids; Thromboxane B2; Tissue Distribution

To study the role of the vasodilatory, antiaggregatory prostacyclin (PGI2) and its endogenous antagonist thromboxane A2 (TxA2) in acute pancreatitis, we measured serum thromboxane B2 (TxB2, which indicates platelet TxA2 production) and plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha, which indicates systemic PGI2 production) from sequential blood samples in trypsin and taurocholate induced acute canine hemorrhagic pancreatitis (AHP). In addition the effect of a prostaglandin synthesis inhibitor, ibuprofen, was studied and systemic (MAP) and pulmonary artery pressure (MPAP) were recorded for 4.5 hr. The animals were divided into a sham-operated group, an AHP group, an ibuprofen prophylaxis group, and an ibuprofen therapy group. In the sham group the parameters remained stable throughout the experiment. In the AHP group MAP decreased steadily and 6-keto-PGF1 alpha rose significantly from 80.0 +/- 7.8 to 956.0 +/- 287.0 pg/ml (P less than 0.001), whereas serum TxB2 and MPAP remained unchanged. Ibuprofen prophylaxis eliminated the initial fall in MAP and the rise of 6-keto-PGF1 alpha. Ibuprofen therapy normalized the initially decreased MAP and depressed the level of 6-keto-PGF1 alpha. We conclude that PGI2 may at least partly mediate the initial hypotension in canine AHP, whereas platelet TxA2 production obviously has a negligible role in the development of hemodynamic changes in AHP.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Blood Pressure; Dogs; Epoprostenol; Hemorrhage; Ibuprofen; Pancreatitis; Thromboxane B2

The ability of plasma to support prostacyclin like activity from human umbilical arterial rings was studied in 17 patients with Henoch-Schönlein purpura and 17 controls matched for age and sex. Plasma from 13 of the 17 patients showed a diminished or absent ability to support prostacyclin like activity in vitro. Six patients whose plasma had a low or absent ability to support prostacyclin like activity showed evidence of inhibitory activity. Plasma from three of these patients also failed to preserve the effect of a stable prostacyclin like analogue (ZK36-374). The plasma concentration of prostacyclin metabolite and the serum concentration of thromboxane A2 metabolite, thromboxane B2, were measured simultaneously. The concentration of plasma prostacyclin metabolite in 10 of the 14 patients was decreased, and a positive correlation was found between the plasma prostacyclin metabolite values and the ability of the plasma to support prostacyclin like activity. There was no significant difference in the serum thromboxane A2 metabolite concentrations between the patients and controls. These data suggest that abnormalities of vascular prostaglandin metabolism are involved in the pathophysiology of Henoch-Schönlein purpura.

Topics: Acute Disease; Adolescent; Child; Child, Preschool; Epoprostenol; Humans; IgA Vasculitis; Iloprost; Muscle, Smooth, Vascular; Thromboxane B2

Carrageenin pleurisy was induced in adrenalectomised (ADX) and sham-operated (SHO) rats. The magnitude and duration of inflammation, as estimated by fluid exudation and cell migration, was greatly increased (approximately doubled) in ADX rats compared with that in their SHO controls. The content of eicosanoids (6-keto-prostaglandin F1 alpha (6-keto-PGF 1 alpha), thromboxane B2 (TXB2), and leukotriene B4 (LTB4] in inflammatory exudates from ADX rats was significantly (2-4 fold) greater than that of their SHO controls. Resident macrophages obtained from ADX rats produced more eicosanoids per cell per unit time when stimulated in vitro with zymosan, than did cells from the SHO controls. Administration of glucocorticoids blocked the inflammatory response and reduced the release of eicosanoids both in vitro and in vivo in both groups of rats. These data are consistent with the notion that physiological amounts of glucocorticoids exert a tonic inhibitory action on phospholipase activity in normal animals and that the increased secretion of these hormones during the inflammatory response serves to check and control the development of inflammation.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adrenalectomy; Animals; Annexins; Carrageenan; Glucocorticoids; Glycoproteins; In Vitro Techniques; Inflammation; Leukotriene B4; Phospholipases A; Pleurisy; Rats; Thromboxane B2

We examined changes in the levels of eicosanoids in blood and pulmonary lymph of anesthetized sheep undergoing acute anaphylaxis. Within 1-3 min of intravenous antigenic challenge of previously sensitized sheep, there were approximately 7-30-fold elevations in mean arterial plasma levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha, respectively, as measured by RIA. Negligible changes in levels of these cyclooxygenase products were found in both nonsensitized sheep and in sensitized sheep treated with indomethacin before antigenic challenge. In contrast, no changes in levels of sulfidopeptide leukotrienes (SPLT) in pulmonary lymph were detectable by RIA during anaphylaxis in sensitized or nonsensitized sheep, but levels of SPLT in indomethacin-treated sensitized sheep increased more than fivefold above levels in lymph from both other groups of animals. The immunoreactive SPLT in lymph from indomethacin-treated sheep was accounted for as LTE4, as demonstrated by mobility on HPLC and absorbance at 280 nm. These results support the possibility that certain undesirable effects of nonsteroidal antiinflammatory drugs, such as cardiopulmonary reactions in aspirin-sensitive individuals, and impaired renal and cardiac function during therapy with these drugs, may be related in part to augmented synthesis of the 5-lipoxygenase pathway products, especially those of the sulfidopeptide class. Increased LT production could also limit the antiinflammatory effectiveness of these drugs in many disease states.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Anaphylaxis; Animals; Anti-Inflammatory Agents; Arachidonate Lipoxygenases; Arachidonic Acid; Arachidonic Acids; Cyclooxygenase Inhibitors; Indomethacin; Leukotriene E4; Lipoxygenase; Lung; Lymph; Prostaglandin-Endoperoxide Synthases; Sheep; SRS-A; Thromboxane B2

Evidence suggests that changes in prostaglandins and disseminated intravascular coagulation accompany pancreatitis. Both may induce changes in platelet function. We wished to determine if experimentally induced pancreatitis in the dog was associated with altered platelet number and function, and whether there were concomitant changes in prostaglandins. Evidence for disseminated intravascular coagulation in the dogs with pancreatitis were red blood cell fragmentation, increased platelet turnover indicated by macro-platelets and the transient presence of fibrin degradation products in urine. There were no significant changes in platelet count. The platelets from dogs with pancreatitis showed a functional defect characterized by significantly decreased aggregation in response to adenosine diphosphate, arachidonic acid, and collagen. Release of adenosine triphosphate from platelets was reduced in collagen-stimulated aggregation. There were no changes in the plasma concentrations of thromboxane B2, 6-Keto-PGF1a, and PGE2. This defect may have been due to the generation of fibrin degradation products and platelet "exhaustion".

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adenosine Diphosphate; Animals; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Collagen; Dinoprostone; Dogs; Fibrin Fibrinogen Degradation Products; Fluid Therapy; Hematocrit; Pancreatitis; Platelet Aggregation; Platelet Count; Prostaglandins; Prostaglandins E; Thromboxane B2

Topics: Acute Disease; Adult; Aged; Cerebral Infarction; Female; Humans; Male; Middle Aged; Prognosis; Radioimmunoassay; Thromboxane B2

Topics: Acute Disease; Adult; Aged; Cerebral Hemorrhage; Cerebrovascular Disorders; Female; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Prognosis; Radioimmunoassay; Thromboxane B2

The behavior of two vasoactive prostanoids was studied in experimental acute pancreatitis (AP) in rats. The stable metabolites of prostacyclin (PGI2) and thromboxane A2 (TXA2), 6-keto-PGF1 alpha and TXB2, respectively, were measured during the course of experimental AP. Blood samples were taken at 3, 6, and 8 h after the induction of AP. In AP both plasma 6-keto-PGF1 alpha plasma TXB2 and serum TXB2 increased up to 6 h simultaneously (6-keto-PGF1 alpha from 271.1 +/- 77.2 pg/ml (mean +/- SD) to 459.4 +/- 192.6 pg/ml, plasma TXB2 from 752 +/- 350 pg/ml to 3640 +/- 2160 pg/ml and serum TXB2 from 22.3 +/- 14.8 micrograms/ml to 140.8 +/- 52.8 micrograms/ml). After 6 h 6-keto-PGF1 alpha remained elevated, whereas serum TXB2 dropped significantly. We suggest that in AP the balance of PGI2 and TXA2 is initially maintained, but later on an imbalance appears to favor vasodilatory PGI2. These agents may contribute to the regulation of the blood flow in the pancreas and thus play a role in the pathophysiology of AP.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Male; Pancreatitis; Prostaglandins; Rats; Rats, Inbred Strains; Thromboxane B2

Spontaneous increase in platelet activity and change in coronary vasomotor tone have been implicated in the pathogenesis of acute myocardial ischemia. To define the mechanism of platelet "hypersensitivity" in acute myocardial ischemia, we examined the status of platelet alpha 2-adrenergic receptors in patients hospitalized with severe unstable angina. With the use of the specific alpha 2-receptor antagonist 3H-yohimbine, we identified a 26% decrease in the receptor binding sites on platelet membranes from patients with unstable angina compared with controls (155 +/- 32 vs. 210 +/- 29 fmol/mg protein, P less than or equal to 0.005). The dissociation constants of 3H-yohimbine binding to platelet alpha 2-receptors were similar in both groups (3.3 +/- 1.1 and 4.1 +/- 1.6 nmol/L, P not significant). To study the alterations in the affinity of platelet alpha 2-receptors for the agonists, effects of 1-epinephrine on specific binding of 3H-yohimbine were examined. We observed a marked reduction in 1-epinephrine concentration for inhibition of antagonist binding by 50% in acute myocardial ischemia (IC50: 4.2 +/- 3.9 X 10(-8) vs. 6.7 +/- 3.4 X 10(-7) mol/L, P less than or equal to 0.01), indicating increase in platelet alpha 2-receptor affinity for the agonist. Platelet aggregation and thromboxane A2 generation in response to epinephrine were also significantly increased in the acute phase of myocardial ischemia. This study suggests enhanced affinity of platelet alpha 2-receptors to the agonist 1-epinephrine as a possible mechanism of platelet hypersensitivity in acute myocardial ischemia.

Topics: Acute Disease; Adrenergic alpha-Agonists; Aged; Angina Pectoris; Angina, Unstable; Blood Platelets; Catecholamines; Coronary Disease; Epinephrine; Humans; Male; Middle Aged; Platelet Aggregation; Receptors, Adrenergic, alpha; Thromboxane A2; Thromboxane B2; Yohimbine

The effect of endotoxin tolerance on ocular inflammation was studied in rabbits. A single intravenous (IV) injection of endotoxin (bacterial lipopolysaccharide [LPS]) produced a mild acute iridocyclitis. Repeated daily (five to seven days) IV injections of LPS (5 micrograms extracted from Salmonella typhimurium) led to a state of refractoriness or LPS "tolerance," and ocular inflammation was no longer produced. In contrast to controls, in rabbits tolerant to LPS, IV LPS failed to elevate prostaglandin E2, thromboxane B2, or chemotactic factors in the aqueous humor. Rabbits tolerant to LPS also resisted the increase in vascular permeability normally induced by an ocular reversed passive Arthus reaction. These results demonstrated that LPS tolerance can induce anti-inflammatory effects in the eye.

Topics: Acute Disease; Animals; Antigen-Antibody Complex; Aqueous Humor; Arthus Reaction; Chemotactic Factors; Dinoprostone; Drug Tolerance; Lipopolysaccharides; Prostaglandins E; Rabbits; Salmonella typhimurium; Thromboxane B2; Uveitis, Anterior

Prostaglandin plasma levels are elevated in patients with transient myocardial ischemia. We measured 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane (B2(TXB2) in venous blood of 32 patients with myocardial infarction on the first, third, and seventh days. TXB2 and 6-keto-PGF1 alpha levels in these patients (up to 117 +/- 237 pg/ml and 96 +/- 105 pg/ml mean +/- SD, respectively) differed significantly from levels in normal control subjects (10 +/- 12 pg/ml and 4 +/- 7 pg/ml mean +/- SD, respectively) (p less than 0.01). Prostaglandin values remained elevated from day 1 through day 7. In most patients, 6-keto-PGF1 alpha levels prevailed over those of TXB2. In a subgroup suffering from cardiac arrhythmias, the ratio of 6-keto-PGF1 alpha/TXB2 was inverse. It is concluded that prostaglandin generation is increased for at least 7 days after myocardial infarction. A disturbed ratio of 6-keto-PGF1 alpha/TXB2 in favor of the latter might be associated with cardiac arrhythmias in myocardial infarction.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adult; Aged; Arrhythmias, Cardiac; Epoprostenol; Female; Humans; Male; Middle Aged; Myocardial Infarction; Prostaglandins; Thromboxane A2; Thromboxane B2

Platelet aggregation and thromboxane synthesis and platelet sensitivity to the antiaggregatory action of prostaglandin I2 were studied serially in a subject suffering from adult hemolytic-uremic syndrome. Platelet aggregation in vitro was defective during the acute phase of the disease and recovered during the convalescent phase. Defective aggregation was not associated with a failure of thromboxane synthesis although it was related to an intrinsic platelet defect rather than an inhibitor in the plasma. The platelets were insensitive to prostaglandin I2, even in the recovery phase of the disease. Furthermore, plasma from the patient rendered normal platelets insensitive to prostaglandin I2 and more sensitive to aggregating agents. It is concluded that the platelet abnormality in hemolytic-uremic syndrome is complex and it combines both an intrinsic platelet abnormality and a plasma component.

Topics: Acute Disease; Drug Resistance; Epoprostenol; Female; Hemolytic-Uremic Syndrome; Humans; In Vitro Techniques; Middle Aged; Platelet Aggregation; Thromboxane B2

Prostacyclin (PGI2), a potent vasodilator with complex effects on the mesenteric circulation, has been found to be elevated in the hemorrhagic ascitic fluid of pigs with hemorrhagic pancreatitis. This investigation was designed to determine if blockage of PGI2 significantly reduces the volume and/or toxicity of hemorrhagic ascitic fluid associated with hemorrhagic pancreatitis in pigs. Fifteen pigs were studied: five received corticosteroids, five received ibuprofen, and five were untreated. The relative toxicity of the hemorrhagic ascitic fluid was assessed by intraperitoneal injections of the fluid from pigs into mice.. (1) hemorrhagic pancreatitis was associated with high levels of PGI2 in blood 15 times and in hemorrhagic ascitic fluid 25 times that of baseline; (2) steroids and ibuprofen blocked PGI2 production (p less than 0.05); (3) neither steroids nor ibuprofen, even when administered as pretreatment, decreased ascites formation; and (4) the mortality rate in mice was significantly reduced (p less than 0.05) in the ibuprofen-treated group as compared with the untreated and steroid-treated groups.. PGI2 does not play a significant role in the volume of ascites formation. There was an absence of toxicity in the hemorrhagic ascitic fluid of the ibuprofen-treated group.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Ascitic Fluid; Biological Assay; Electrolytes; Epoprostenol; Female; Hemorrhage; Hydrogen-Ion Concentration; Ibuprofen; Methylprednisolone; Mice; Osmolar Concentration; Pancreatitis; Swine; Thromboxane B2

Concentrations of prostaglandin F2 alpha (PGF2 alpha) and thromboxane B2 (TXB2) were evaluated in the milk of cows with naturally occurring (n = 3) and experimentally induced (n = 5) acute coliform mastitis. These arachidonic acid metabolites were measured by radioimmunoassay in unextracted milk. Experimental infections were induced by inoculating 600 to 1,200 colony-forming units of Escherichia coli into 1 mammary quarter per experimental cow. In the experimental cows, milk was collected before inoculation and at 12, 24, 36, 48, 60, and 72 hours after inoculation. Somatic cell concentrations, bovine serum albumin, and concentrations of PGF2 alpha and TXB2 were determined in milk collected at each sampling. Mild-to-moderate increases in milk PGF2 alpha and TXB2 concentrations were observed in cows with naturally occurring mastitis. the increases corresponded to the clinical severity and course of mastitis. In the experimental cows, increases in milk PGF2 alpha and TXB2 concentrations were observed, but the increases were not significant, using a statistical model that included factors of treatment, cows, hours after inoculation, cows-by-treatment and hours-by-treatment interactions, and random error (residual). Results of the present study indicated a large biological variability in milk arachidonic acid metabolite concentrations in cows with acute coliform mastitis, and that arachidonic acid metabolites may be important in the pathophysiologic process of acute coliform mastitis.

Topics: Acute Disease; Analysis of Variance; Animals; Arachidonic Acid; Arachidonic Acids; Cattle; Dinoprost; Escherichia coli Infections; Female; Lactation; Mastitis, Bovine; Milk; Pregnancy; Prostaglandins F; Radioimmunoassay; Thromboxane B2; Thromboxanes

An early event in the evolution of acute respiratory failure (ARF) is thought to be the activation of platelets, their pulmonary entrapment and subsequent release of the smooth muscle constrictor serotonin (5HT). This study tests the thesis that inhibition of 5HT will improve lung function. The etiology of ARF in the 18 study patients was sepsis (N = 10), aspiration (N = 3), pancreatitis (N = 1), embolism (N = 2), and abdominal aortic aneurysm surgery (N = 2). Patients were divided into two groups determined by whether their period of endotracheal intubation was less than or equal to 4 days (early ARF, N = 12) or greater than 4 days (late ARF, N = 6). Transpulmonary platelet counts in the early group showed entrapment of 26,300 +/- 5900 platelets/mm3 in contrast to the late group where there was no entrapment (p less than 0.05). The platelet 5HT levels in the early group were 55 +/- 5 ng/10(9) platelets, values lower than 95 +/- 15 ng/10(9) platelets in the late ARF group (p less than 0.05), and 290 +/- 70 ng/10(9) platelets in normals. The selective 5HT receptor antagonist, ketanserin was given as an intravenous bolus over 3 minutes in a dose of 0.1 mg/kg, followed by a 30-minute infusion of 0.08 mg/kg. During this period mean arterial pressure (MAP) fell from 87 +/- 5 to 74 +/- 6 mmHg (mean +/- SEM) (p less than 0.05). One and one-half hours following the start of therapy, MAP returned to baseline. At this time, patients with early ARF showed decreases in: physiologic shunt (Qs/QT) from 26 +/- 3 to 19 +/- 3 (p less than 0.05); peak inspiratory pressure from 35 +/- 2 to 32 +/- 2 cmH2O (p less than 0.05) and in mean pulmonary arterial pressure from 32 +/- 2 to 29 +/- 1 mmHg (p less than 0.05). At 4 hours all changes returned to baseline levels. In early ARF ketanserin did not alter pretreatment values of: pulmonary arterial wedge pressure, 17 +/- 3 mmHg; cardiac index, 2.8 +/- 0.3 L/min X m2; platelet count, 219,000 +/- 45,000/mm3; platelet 5HT, 55 +/- 5 ng/10(9) platelets; plasma 5HT, 142 +/- 21 ng/ml; plasma thromboxane B2, 190 +/- 30 pg/ml; or plasma 6-keto-PGF1 alpha, 40 +/- 10 pg/ml. Ketanserin infusion in patients with late ARF yielded no benefit. In both ARF groups the decreases in QS/QT were inversely related to the duration of intubation (r = 0.70; p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adult; Aged; Blood Platelets; Blood Pressure; Cardiac Output; Female; Humans; Intubation, Intratracheal; Ketanserin; Male; Middle Aged; Piperidines; Platelet Count; Pulmonary Wedge Pressure; Respiratory Function Tests; Respiratory Insufficiency; Serotonin; Serotonin Antagonists; Thromboxane B2

Blockade of the arachidonic acid cascade has been shown to improve survival and hemodynamic alterations in animal models of sepsis and acute respiratory failure (ARF). The effects of intravenous ibuprofen, a cyclooxygenase inhibitor, were observed in 20-30 kg pigs with ARF induced by a continuous LD100 infusion of live Pseudomonas aeruginosa (2 X 10(8)/20 kg/min). Cardiopulmonary parameters were monitored in animals intubated, paralyzed, and ventilated at a 250-ml tidal volume and 0.5 FiO2. Pigs were randomly assigned to three groups: Group I received 2 bolus infusions of ibuprofen (12.5 mg/kg) at 20 and 210 min after baseline; Group II had Ps. aeruginosa (2 X 10(8) CFU/20 kg/min) only; Group III received Ps. aeruginosa and 12.5 mg/kg of ibuprofen at 20 and 210 min of ARF. Ibuprofen alone caused no significant changes in cardiorespiratory parameters. With Ps. aeruginosa infusion, significant pulmonary hypertension, hypoxemia, increased intrapulmonary shunt fraction, and systemic hypotension occurred. In the septic animals treated with ibuprofen, oxygenation was improved by a significant decrease in shunt, pulmonary edema, and pulmonary hypertension.

Topics: Acute Disease; Animals; Disease Models, Animal; Hemodynamics; Ibuprofen; Lung; Male; Pseudomonas Infections; Respiratory Insufficiency; Swine; Thromboxane B2

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

Acute thrombosis was induced in the carotid arteries of anaesthetised rabbits by local electrical stimulation (1mA for 2 min) of the vessel wall. Histological findings confirmed the platelet-rich composition of the thrombus. Platelet accumulation at the stimulus site was quantitated with "'Indium-labelling of autologous platelets. In rabbits injected intravenously with either 2 mg/kg dazoxiben or 10 mg/kg aspirin, accumulation of labelled platelets was considerably reduced. Animals which received vehicle injection only, showed no such reduced thrombus formation. In separate experiments in anaesthetised rabbits, the levels of TxB2 and 6KPGF1 alpha in clotting blood were measured in blood samples taken from animals which had received the above drug treatments. Aspirin markedly reduced the production of both arachidonate metabolites. In contrast, dazoxiben almost totally inhibited TxB2 production but caused a 3.5 fold increase in the levels of 6KPGF1 alpha. These findings demonstrate an anti-thrombotic effect and confirm the mechanistic selectivity of a thromboxane synthetase inhibitor.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Aspirin; Carotid Artery Thrombosis; Cells, Cultured; Enzyme Inhibitors; Fibrinolytic Agents; Imidazoles; In Vitro Techniques; Oxidoreductases; Platelet Aggregation; Rabbits; Thromboxane B2; Thromboxane-A Synthase

Immunoreactive thromboxane B2 (i-TXB2) was measured in daily urine samples from twelve patients after renal transplantation. In 21 of 30 rejection episodes, the increase in i-TXB2 preceded both the increase in serum beta 2-microglobulin (beta 2-MG) and the clinical diagnosis of rejection. In 26 of 30 rejection episodes, the increase in urine i-TXB2 preceded the increase in serum creatinine. The degree of change in i-TXB2 is greater than that of either serum beta 2-MG or creatinine. Urinary i-TXB2 was very high in one patient with deep venous thrombosis, but it did not rise in patients with urinary tract infection, pneumonia, or acute tubular necrosis. Thus, urinary i-TXB2 seems to be an early indicator of clinical renal allograft rejection.

Topics: Acute Disease; Adult; Aged; beta 2-Microglobulin; Creatinine; Female; Graft Rejection; Humans; Kidney Transplantation; Male; Middle Aged; Prognosis; Radioimmunoassay; Thromboxane B2; Thromboxanes; Transplantation, Homologous