thromboxane-a2 and Syndrome

The early period following an acute coronary syndrome (ACS) is characterised by atherosclerotic plaque destabilisation and a pro-coagulant state, and is when patients are at highest risk for recurrent cardiovascular events and mortality. Statins decrease thrombus formation and increase fibrinolysis, inhibit platelet reactivity and aggregation, improve endothelial function in patients with coronary artery disease and have a major role in plaque stabilisation. Several studies showed that initiation of early statin therapy in these settings may have beneficial effects. This review summarises the current data on statins in the setting of ACSs. Known and other possible mechanisms of action are described. The pathophysiological mechanisms, histological features and biochemical characteristics of ACS are different than those with stable coronary disease, thereby suggesting that the mechanisms whereby statins exert their benefits in ACS may be distinct from those for stable CHD. Initiation of the therapy during hospitalisation rather than at the time of hospital discharge may provide protection against early recurrent cardiovascular events and also improve patients' compliance.

Topics: C-Reactive Protein; Cholesterol, LDL; Clinical Trials as Topic; Coronary Artery Disease; Dose-Response Relationship, Drug; Endothelium, Vascular; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Ischemia; Platelet Aggregation Inhibitors; Risk Factors; Syndrome; Thromboxane A2

A severe case of preeclampsia with Hellp Syndrome is reported. Clinical findings, laboratory abnormalities and pathogenesis, were discussed. We concluded that severe preeclampsia and Hellp Syndrome are not different diseases, but the natural course of preeclampsia per se.

Topics: Adult; Anemia, Hemolytic; Anticonvulsants; Antihypertensive Agents; Cesarean Section; Combined Modality Therapy; Epoprostenol; Female; Humans; Incidence; Liver Diseases; Pre-Eclampsia; Pregnancy; Syndrome; Thrombocytopenia; Thromboxane A2; Vasoconstriction

Topics: Blood Coagulation Disorders; Blood Platelet Disorders; Blood Platelets; Heterozygote; Humans; Platelet Aggregation; Syndrome; Thromboxane A2; Thromboxanes; von Willebrand Diseases

Arachidonic acid metabolites, especially thromboxane-A2 and prostacyclin, have been shown to be increased in experimental models of sepsis and the adult respiratory distress syndrome (ARDS) and play a major pathophysiologic role. This study was designed to determine if these metabolites are increased in human sepsis syndrome and if inhibition of fatty acid cyclooxygenase affects their formation and their pathophysiologic sequelae. We conducted a double-blind, placebo-controlled trial of ibuprofen (800 mg given rectally every 4 h for three doses) in 30 patients with sepsis syndrome defined by abnormal vital signs, the appearance of serious infection, and at least one major organ failure. Urinary concentrations of the metabolite of thromboxane-A2, 2,3-dinor-TxB2, and prostacyclin, 2,3-dinor-6-keto-prostaglandin F2 alpha, were elevated 10 to 20 times normal and declined to four to five times normal by 12 h after entry in the ibuprofen-treated group and remained elevated in the placebo-treated patients. The urinary concentration of TxB2 and 6-keto-prostaglandin F1 alpha, which reflect renal production of TxA2 and prostacyclin, respectively, were also increased approximately 10-fold over normal and were subsequently decreased by ibuprofen. Coincident with the reduction in metabolite levels, the ibuprofen-treated group, but not the placebo-treated group, experienced a significant decline in temperature, heart rate, and peak airway pressure, and a trend towards more rapid reversal of shock (p = 0.12).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cyclooxygenase Inhibitors; Double-Blind Method; Epoprostenol; Humans; Ibuprofen; Multiple Organ Failure; Sepsis; Syndrome; Thromboxane A2; Time Factors

Aspirin-like defect (ALD) is a rare, mostly autosomal dominant inherited dysfunction of the intraplatelet arachidonic acid (AA) pathway leading to impaired thromboxane A2 signalling. We aimed to establish diagnostic criteria for ALD diagnosis and present clinical and laboratory phenotypes of 52 individuals from 17 unrelated families. Platelet in vitro function was determined on the basis of platelet aggregation response (PAR) to AA, adenosine diphosphate, collagen and ristocetin as well as PFA-100 closure times (CT). Using impaired PAR to AA (< or =10%) as the mandatory diagnostic criterion, ALD could be confirmed in 17 patients. Subsequently, family members were investigated and among 35 individuals an additional 13 ALD patients as well as 4 individuals with mild ALD (PAR to AA: 19-32%) were identified. At least one bleeding symptom was reported by 25 (74%) ALD patients and prolonged CT was detected in 24 (71%) of the cases, both significantly correlated with impaired PAR to AA (P = 0.001 and P = 0.002, respectively). An estimated 0.6% prevalence was determined for ALD in our paediatric patients with suspected coagulation disorders. Due to the mild bleeding symptoms, ALD is probably underdiagnosed. If ALD is suspected, PAR to AA is suitable for the identification of individuals at risk of increased haemorrhage.

Topics: Adolescent; Adult; Arachidonic Acid; Bleeding Time; Blood Platelet Disorders; Blood Platelets; Case-Control Studies; Chi-Square Distribution; Child; Child, Preschool; Female; Hemostatic Disorders; Humans; Male; Middle Aged; Phenotype; Platelet Aggregation; Platelet Function Tests; Prostaglandin-Endoperoxide Synthases; Signal Transduction; Syndrome; Thromboxane A2; Young Adult

Studying consanguineous families with Ghosal hematodiaphyseal dysplasia syndrome (GHDD), a disorder of increased bone density, we identified mutations in TBXAS1, which encodes thromboxane synthase (TXAS). TXAS, an enzyme of the arachidonic acid cascade, produces thromboxane A(2) (TXA(2)). Platelets from subjects with GHDD showed a specific deficit in arachidonic acid-produced aggregation. We also found that TXAS and TXA(2) modulated expression of TNFSF11 and TNFRSF11B (encoding RANKL and osteoprotegerin (OPG), respectively) in primary cultured osteoblasts.

Topics: Amino Acid Substitution; Bone Density; Bone Diseases; Bone Remodeling; Catalytic Domain; Cells, Cultured; Consanguinity; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Humans; Models, Biological; Osteoprotegerin; Point Mutation; RANK Ligand; Syndrome; Thromboxane A2; Thromboxane-A Synthase

To observe the effect of small needle-knife lysis on plasma calcitonin gene-related peptide (CGRP), endothelin (ET), 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), thromboxane A2 (TXA2) contents in rats with experimental third lumbar vertebra transverse process syndrome (TLVTPS) so as to explore its underlying mechanism in clinical treatment.. Forty SD rats were randomly divided into normal control, model, lysis and EA groups. TLVTPS model was established by embedding a piece of gelatin sponge (0.5 cm x 0.5 cm) to the transverse process of the 3rd lumbar vertebra under anesthesia. EA (2/100 Hz, 1-2 mA) was applied to left "Shenshu" (BL23) -"Yaoyangguan" (GV3) for 20 min, once every other day, 6 times altogether. For animals of lysis group, the lysis was performed by using a small needle-knife in the induration spot or cord-like region near the incision, once a week and twice altogether. Four weeks later after modeling, plasma CGRP, ET, 6-keto-PGF1alpha and TXA2 contents were detected by using radioimmunoassay and enzyme linked immunosorbent assay (ELISA).. Compared with normal control group, plasma CGRP, ET, TXA2 and 6-keto-PGF1alpha increased significantly in model group (P<0.01); in comparison with model group, plasma CGRP, TXA2 and 6-keto-PGF1alpha in both EA and lysis groups decreased considerably (P<0.05, 0.01). No significant differences were found between EA and lysis groups in plasma CGRP, ET and 6-keto-PGF1alpha levels (P>0.05).. Both EA and lysis of acupotomology have an adjusting effect on vasoactive substances (CGRP, TXA2 and 6-keto-PGF1alpha) levels in TLVTPS rats, which may contribute to their effects in improving local blood circulation and relieving soft tissue injury in the treatment of third lumbar vertebra transverse process syndrome.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Calcitonin Gene-Related Peptide; Electroacupuncture; Endothelins; Lumbar Vertebrae; Male; Medicine, Chinese Traditional; Rats; Rats, Sprague-Dawley; Spinal Diseases; Syndrome; Thromboxane A2

Bolus i.v. injections of 1.2 N HCl elicit a rapid but transient pulmonary vasoconstriction in broiler chickens. In mammals, the pulmonary vasoconstrictive response to bolus acid injection depends on increased synthesis of thromboxane A2; however, the vascular responsiveness of domestic fowl to thromboxane previously had not been evaluated. In the present study, we tested the hypothesis that, if HCl triggers pulmonary vasoconstriction by stimulating thromboxane A2 synthesis in broilers, then bolus i.v. injections of the potent thromboxane A2 mimetic U44069 (9,11-dideoxy-9alpha,11alpha-epoxy-methanoprostaglandin++ + F2alpha; 1 micromol/mL; 0.5 mL injected volume) should trigger hemodynamic responses similar to those elicited by HCl (1.2 N; 1.5 mL injected volume). Both HCl and the thromboxane mimetic elicited twofold or greater increases in pulmonary vascular resistance, which in turn increased pulmonary arterial pressure by 50% despite concurrent reductions in cardiac output. The reductions in cardiac output were associated with reductions in stroke volume but not heart rate. The thromboxane mimetic also increased the total peripheral resistance, which minimized the reduction in mean systemic arterial pressure associated with the decrease in cardiac output. In contrast, HCl injections did not increase total peripheral resistance; consequently, the reduction in cardiac output caused the mean systemic arterial pressure to decrease by 30 mm Hg. Mannitol (2.5%; 1.5 mL) was injected i.v. as a volume control, and had no influence on any of the variables. This study provides the first direct evidence that thromboxane is a potent pulmonary vasoconstrictor in broilers, and provides support for the hypothesis that thromboxane mediates the pulmonary vasoconstrictive response to bolus i.v. injections of HCl. The differential response of the systemic vasculature to the thromboxane mimetic and HCl may indicate that cardiopulmonary responses to HCl injections are not mediated solely via thromboxane production. Alternatively, a direct dilatory effect of elevated hydrogen ion concentrations on the systemic vasculature may have counteracted any tendency for simultaneously evolved endogenous thromboxane to elicit systemic vasoconstriction.

Topics: Animals; Chickens; Hydrochloric Acid; Hypertension, Pulmonary; Injections, Intravenous; Lung; Male; Syndrome; Thromboxane A2; Vasoconstriction

As chronic exposure to hand-held vibrating tools may cause endothelial injury, a subsequent sustained platelet activation with the increased release of vasoconstricting thromboxane A2 (TxA2) could be of pathophysiological importance in vibration-induced Raynaud's phenomenon. Therefore, the aim of this study was to elucidate whether or not hand-arm vibration syndrome is accompanied by increased endogenous TxA2 biosynthesis. The study involved 64 men, aged 23-61 years, stratified according to the exposure to vibrating tools, the presence of Raynaud's phenomenon, and smoking habit. Forty of them were car mechanics and 24 were age-matched healthy volunteers who served as controls. The assessment of platelet TxA2 formation in vivo was performed by quantification of the urinary excretion of its major metabolite, 2,3-dinorthromboxane B2 (2,3-dinor-TxB2), employing gas chromatography-mass spectrometry. The average urinary excretion rate of 2,3-dinor-TxB2 in patients with Raynaud's phenomenon was 296 +/- 42 pg/mg creatinine and did not differ significantly from the corresponding values in controls (328 +/- 62 pg/mg creatinine) or individuals exposed to vibrating tools, but without any signs of vasospastic disease (232 +/- 29 pg/mg creatinine). The only statistically significant difference was found between smokers and non-smokers (P < 0.001), a finding confirming the existence of chronic platelet dysfunction in cigarette smokers. The present data indicate that chronic exposure to vibrating tools, with or without Raynaud's phenomenon, is not associated with an enhanced platelet function as monitored by the urinary excretion of 2,3-dinor-TxB2. Hence, a possible vibration-induced vascular injury does not seem to provide a stimulus sufficient to induce a persistent platelet activation.

Topics: Adult; Blood Platelets; Chromatography, Gas; Chromatography, Liquid; Creatinine; Humans; Male; Mass Spectrometry; Middle Aged; Raynaud Disease; Syndrome; Thromboxane A2; Thromboxane B2; Vasoconstriction; Vibration

Topics: Adult; Autoantibodies; Epoprostenol; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Phospholipids; Syndrome; Thromboxane A2

Thirty-one patients with IgG antibodies to cardiolipin (ACLA) were studied to determine their in vivo formation of the platelet aggregating and vasoconstricting substance thromboxane A2 (TxA2) and the platelet inhibiting and vasodilating substance prostacyclin (PGI2). This was done by measurements in urine of their enzymatically formed metabolites 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha, respectively, using gas chromatography-mass spectrometry. It is demonstrated that patients with IgG ACLA have a highly significant increase in the biosynthesis of TxA2 compared with age-matched healthy controls (807 +/- 163 [SEM] vs. 230 +/- 15 pg mg-1 creatinine, P = 0.0000005). A significant increment of the formation of PGI2 was also found (189 +/- 23 (SEM) vs. 125 +/- 11 pg mg-1 creatinine, P = 0.03), although this was much less pronounced than that for TxA2. We conclude that the highly increased formation of TxA2, reflecting platelet activation, in patients with IgG ACLA is of pathophysiologic relevance for their tendency to arterial and venous thrombosis and hence that they should be considered for prophylactic treatment with inhibitors of TxA2 formation, like aspirin.

Topics: Adult; Autoimmune Diseases; Cardiolipins; Epoprostenol; Female; Humans; Male; Middle Aged; Phospholipids; Platelet Activation; Syndrome; Thrombosis; Thromboxane A2

Topics: Diagnosis, Differential; Hemodynamics; Humans; Kidney; Kidney Failure, Chronic; Liver; Liver Cirrhosis; Natriuretic Agents; Oliguria; Prostaglandins; Renal Circulation; Renin-Angiotensin System; Sympathetic Nervous System; Syndrome; Thromboxane A2

The hepatorenal syndrome is considered to be a functional renal failure due to active renal vasoconstriction. The purpose of this work was to study the urinary elimination of prostaglandins and the plasmatic polyunsaturated fatty acid precursors of prostaglandins. The urinary elimination of PGE2 was not significantly different in the groups of patients studied: controls, group I (193 +/- 42 ng/24 h), cirrhotic patients without ascites, group II (274 +/- 43 ng/24 h), cirrhotic patients with ascites, group III (269 +/- 41 ng/24 h). The urinary elimination of PGE1 and PGF2 alpha varied in the same way as PGE2. In cirrhotics with hepatorenal syndrome (group IV) the urinary elimination of vasodilating prostaglandins was greatly decreased (p less than 0.001); PGE2 (53 +/- 16 ng/24 h), PGE1 (65 +/- 11 ng/24 h). The urinary elimination of PGF2 alpha was also decreased (293 +/- 75 ng/24 h). On the other hand, the urinary elimination of thromboxane, a vasoconstrictor, increased progressively from group I (287 +/- 75 ng/24 h) to group IV (980 +/- 266 ng/24 h) (p less than 0.05). Plasmatic arachidonic acid was significantly decreased in group IV (5.0 +/- 0.6 p. 100) compared to group I (10.0 +/- 0.6 p. 100) (p less than 0.001), to group II (10.3 +/- 0.5 p. 100) (p less than 0.001), and to group III (8.5 +/- 0.7 p. 100) (p less than 0.05). In conclusion, in hepatorenal patients, urinary excretion of a vasoconstricting prostaglandin (thromboxane) is increased while urinary excretion of vasodilating prostaglandins is decreased. This decrease could be secondary to a lack of plasmatic arachidonic acid, precursor of prostaglandins.

Topics: Acute Kidney Injury; Ascites; Fatty Acids, Unsaturated; Humans; Kidney Diseases; Liver Cirrhosis; Prostaglandins; Syndrome; Thromboxane A2; Thromboxanes