No abstract available.
Dinoprost* ; Flurbiprofen* ; Gabexate* ; Prednisolone* ; Thromboxane B2*

Aspirin resistance defined by light transmittance aggregometry (LTA) or urinary 11-dehydro-thromboxane B2 has been associated with an increased risk of adverse clinical events. However, aspirin resistance based on the point-of-care VerifyNow-Aspirin assay (aspirin reaction unit > or = 550) shows poor sensitivity compared with LTA. In aspirin-treated patients, activation by cyclooxygenase- independent pathways may be associated with residual platelet reactivity, which may cause adverse clinical outcomes in some portion. A large-scale, prospective study using several platelet function assays should be performed to establish the long-term clinical significance of antiplatelet resistance in Korean patients treated with coronary stenting. Accordingly, we can apply tailored antiplatelet therapy in resistant patients.
Aspirin ; Blood Platelets ; Humans ; Light ; Prospective Studies ; Stents ; Thromboxane B2

The inhibitory effects of perilla oil on the platelet aggregation in vitro and thrombosis in vivo were investigated in comparison with aspirin, a well-known blood flow enhancer. Rabbit platelet-rich plasma was incubated with perilla oil and aggregation inducers collagen or thrombin, and the platelet aggregation rate was analyzed. Perilla oil significantly inhibited both the collagen- and thrombin-induced platelet aggregations, in which the thromboxane B2 formation from collagen-activated platelets were reduced in a concentration-dependent manner. Rats were administered once daily by gavage with perilla oil for 1 week, carotid arterial thrombosis was induced by applying 35% FeCl3-soaked filter paper for 10 min, and the blood flow was monitored with a laser Doppler probe. Perilla oil delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at 0.5 mL/kg. In addition, a high dose (2 mL/kg) of perilla oil greatly prevented the occlusion, comparable to the effect of aspirin (30 mg/kg). The results indicate that perilla oil inhibit platelet aggregation by blocking thromboxane formation, and thereby delay thrombosis following oxidative arterial wall injury. Therefore, it is proposed that perilla oil could be a good candidate without adverse effects for the improvement of blood flow.
Animals ; Aspirin ; Blood Platelets* ; Collagen ; Perilla* ; Platelet Aggregation* ; Platelet-Rich Plasma ; Rats ; Thrombin ; Thrombosis* ; Thromboxane B2

To evaluate the cause of intraocular pressure elevation and the effect of indomethacin after Nd:YAG laser anterior capsulotomy in rabbit authors measured the intraocular pressure, prostaglandin E2 and thromboxane B2 concentrations of aquous humor, and observed the morphological change of trabecular meshwork using scanning electron microscope in indomethacin pretreatment (group I) and non-treatment (group II) group. The intraocular pressure and the concentrations of prostaglanding E2 and thromboxane B2 in group II were higher than in group I. And the scanning electron microscopy showed inflammatory reaction in group II. These results support that the causes of intraocular pressure elevation are elevation of prostaglandin E2. thromboxane B2 concentrations in aqueous humor and intraocular inflammation secondary to it.
Aqueous Humor ; Dinoprostone ; Indomethacin* ; Inflammation ; Intraocular Pressure ; Microscopy, Electron, Scanning ; Rabbits* ; Thromboxane B2 ; Trabecular Meshwork

To evaluate the cause of intraocular pressure elevation and the effect of indomethacin after Nd:YAG laser anterior capsulotomy in rabbit authors measured the intraocular pressure, prostaglandin E2 and thromboxane B2 concentrations of aquous humor, and observed the morphological change of trabecular meshwork using scanning electron microscope in indomethacin pretreatment (group I) and non-treatment (group II) group. The intraocular pressure and the concentrations of prostaglanding E2 and thromboxane B2 in group II were higher than in group I. And the scanning electron microscopy showed inflammatory reaction in group II. These results support that the causes of intraocular pressure elevation are elevation of prostaglandin E2. thromboxane B2 concentrations in aqueous humor and intraocular inflammation secondary to it.
Aqueous Humor ; Dinoprostone ; Indomethacin* ; Inflammation ; Intraocular Pressure ; Microscopy, Electron, Scanning ; Rabbits* ; Thromboxane B2 ; Trabecular Meshwork

OBJECTIVE: To investigate the antithrombotic effects of recombinant hirudin and its mechanism. METHODS: Sixty male Kunming mice were randomly divided into 6 group (=10):control group, model group, aspirin (25 mg/kg) group, recombinant hirudinlow, middle and high dose (0.05, 0.1, 0.2 mg/kg) groups.Except mice in control group, 2.5 mg/kg carrageenan was injected intraperitoneallyto mice in the other groups to produce thrombosis on the mice tail. The mice in aspirin group were administrated intraperitoneally 25 mg/kg aspirin, the mice in recombinant hirudinlow, middle and high dose groups were administrated intraperitoneally 0.05, 0.1, 0.2 mg/kg combinanthirudin, the mice in control group and model group were administrated intraperitoneallynormal saline at the same volume respectively at 24 h, 0.5 h before injecting carrageenan and 24 h after injecting carrageenan. The black tail length of mice and the incidence of black tail were observed at 48h after injection of carrageenan; prothrombin time (PT), activated partial thromboplastin time (APTT), tissue plasminogen activator (t-PA), type-1 plasminogen activator inhibitor (PAI-1), 6-keto-PGF1α, and thromboxane B2 (TXB2) level in mice plasma were determined. RESULTS: As compared with control group, the mice in model group presented tail thrombosis; PT level in plasma was significantly shortened (<0.01), PAI-1 and TXB2levels in plasma were significantly increased (<0.01), while the t-PA and 6-keto-PGF1α levels in plasma in model group were significantly decreased (<0.01). As compared with model group, the thrombus length in the tail was significantly shortened (<0.05, <0.01), PT level was obviously prolonged (<0.01), and the plasma levels of PAI-1 and TXB2 were significantly decreased (<0.01), while the plasma levels of t-PA and 6-keto-PGF1α were significantly increased (<0.01)in the mice of recombinant hirudin low dose, middle dose, high dose groups and aspirin group. As compared with aspirin group, the thrombus length in the tail was significantly increased (<0.05), PT level was obviously shortened (<0.01), and the plasma levels of PAI-1 and TXB2 were significantly increased (<0.01)in the mice of recombinant hirudin low dose group; the plasma level of 6-keto-PGF1α was significantly decreased (<0.01, <0.05) in the mice of recombinant hirudin low dose and middle dose groups; the plasma levels of PAI-1 and TXB2 were significantly increased (<0.01, <0.05)in the mice of recombinant hirudin middle dose group. CONCLUSIONS The recombinant hirudin can fight against thrombosis, its antithrombotic mechanisms may be related to its influence on the exogenous coagulation system and the promotion of fibrinolysis function.
Animals ; Blood Coagulation ; Fibrinolytic Agents ; Hirudins ; pharmacology ; Male ; Mice ; Recombinant Proteins ; Thromboxane B2 ; Tissue Plasminogen Activator

OBJECTIVETo investigate the dynamic changes of plasma levels of prostacycline (PGI2) and thromboxane A2 (TXA2) and their relationship with the severity of hepatic injury in rats with nonalcoholic fatty liver disease (NAFLD).

METHODSWe established a NAFLD model, with a fat-rich diet consisting of 10% lard oil + 2% cholesterol, which was given to Sprague-Dawley rats (n=48) for a period of 8, 12, 16 and 24 weeks. The other rats were fed standard diets and were used as normal controls (n=24). At sacrifice, liver pathology scores were evaluated and plasma levels of PGI2, its stable metabolic product 6-keto-PGF1 alpha and TXA2, and TXB2 were determined by radioimmunoassay.

RESULTSSimple fatty livers were observed in the model group at 8 weeks. From 12 weeks to 24 weeks, the livers gradually progressed from simple steatohepatitis to liver fibrosis. Plasma levels of TXB2 in the model group increased higher than in the control group after 8 weeks [(52.4+/-3.15) ng/L vs (41.1+/-1.45) ng/L] and continued to increase over time, with the highest levels at 24 weeks [(117.7+/-7.47) ng/L]. A strong positive correlation (r=0.537) was seen between plasma TXB2 levels and the severity of liver injury. Plasma 6-keto-PGF1 alpha concentrations decreased in the model group in comparison with the control group after 8 weeks [(31.1+/-1.62) ng/L vs (36.5+/-1.68) ng/L] and continued to decrease over time, with the lowest concentrations at 24 weeks [(3.4+/-2.43) ng/L t=3.77]. A negative correlation was shown between the 6-keto-PGF1 alpha level and the severity of the liver injury.

CONCLUSIONA rat model of NAFLD was established successfully by feeding a fat-rich diet for 24 weeks. In this model, the imbalance of plasma PGI2 and TXA2 levels (increased TXB2 and decreased 6-keto-PGF1 alpha levels) may play a role in the pathogenesis of experimental NAFLD.

6-Ketoprostaglandin F1 alpha ; blood ; Animals ; Epoprostenol ; blood ; Fatty Liver ; blood ; Liver ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Thromboxane A2 ; blood ; Thromboxane B2 ; blood

BACKGROUND: Thromboxane A2 and endothelin-1 are the potent vasoconstrictors affecting pulmonary pathophysiology in response to whole body inflammatin following CPB. Aprotinin, as an antiiflammatory agent, may decrease the release of such vasoactive substance from pulmonary tissues, preventing pulmonary hypertension after cardiopulmonary bypass. MATERIAL AND METHOD: Ten mongrel dogs(Bwt. ac. 20kg) were subjected to cardioupulmonary bypass for 2 hours and postbypass pulmonary vascular resistance(0, 1, 2, 3 hours) were compared with prebypass level. The dogs were divided into 2 groups; control group(n-5) and aprotinin group(n=5). In the aprotinin group, aprotinin was administered as follows; 50,000 KIU/kg mixed in pump priming solution, 50,000 KIU/kg prebypass intravenous infusion over 30 minutes, 10,000 KIU/kg/hour postbypass continuous infusion. Prebypass and postbypass 0, 1, 2, 3 hour pulmonary vascular resistance were measured. At prebypass and postbypass 0, 90, 180 minutes, blood samples were obtained from pulmonary arterial and left atrial catherers for the assay of plasma thromboxane B2 a stable metabolite of thromboxane A2, and endothelin-1 concentrations. RESULT: The ratios of pustbypass over prebypass pulmonary vascular at postbypass 0, 1, 2, 3 hours were 1.28+/-0.20, 1.82+/-0.23, 1.90+/-0.19, 2.14+/-0.18 in control group, 1.58+/-0.18, 1.73+/-0.01, 1.66+/-0.10, 1.50+/-0.08 in aprotinin group ; the ratios gradually increased in control group while decreased or fluctuated after postbypass 1 hour in aprotinin group. There was statistically significant difference between control group and aprotinin group at postbypass 3 hours(P=0.014). Pulmonary arterial plasma concentration of thromboxane B2(pg/ml) at prebypass, postbypass 0, 90, 180 minutes were 346.4+/-61.9, 529.3+/-197.6, 578.3+/-255.8, 493.3+/-171.3 in control group, 323.8+/-118.0, 422.6+/-75.6, 412.3+/-59.9, 394.5+/-154.0 in aprotinin group. Left atrial concentrations were 339.3+/-89.2, 667.0+/-65.7, 731.2+/-192.7, 607.5+/-165.9 in control group, 330.0+/-111.2, 468.4+/-190.3, 425.4+/-193.6, 4.7.3+/-142.8 in aprotinin group. These results showed decrement of pulmonary thromboxane A2 generation in aprotinin group. Pulmonary arterial concentrations of endothelin-1(fmol/ml) at the same time sequence were 7.84+/-0.31, 13.2+/-0.51, 15.0+/-1.22, 16.3+/-1.73 in control group, 7.76+/-0.12, 15.3+/-0.71, 22.6+/-6.62, 14.9+/-1.11 in aprotinin group. Left atrial concentrations were 7.61+/-17.2, 57.1+/-28.4, 18.9+/-18.2, 31.5+/-20.5 in control group, 5.61+/-7.61, 37.0+/-26.2, 28.6+/-21.7, 37.8+/-30.6 in aprotinin group. These results showed that aprotinin had no effect on plasma endothelin-1 concentration after cardiopulmonary bypass. CONCLUSIONS: Administration of aprotinin during cardiopulmonary bypass could attenuate the increase in pulmonary vascular resistance after bypass. Inhibition of pulmonary thromboxane A2 generation was thought to be one of the mechanism of this effect. Aprotinin had no effect on postbypass endothelin-1 concentration.
Animals ; Aprotinin* ; Cardiopulmonary Bypass ; Dogs ; Endothelin-1* ; Endothelins ; Extracorporeal Circulation* ; Hypertension, Pulmonary ; Infusions, Intravenous ; Plasma* ; Thromboxane A2 ; Thromboxane B2* ; Vascular Resistance ; Vasoconstrictor Agents

Cyclosporine A(CsA) induced nephrotoxicity is a common clinical problem in the patients who underwent organ transplantation and subsequent immunosuppressive therapy. The precise pathophysiology of CsA induced nephrotoxicity still remains uncertain though many hypothesized mechanisms were reported. Therefore, no effective strategy is currently available to counter the nephrotoxic effects of CsA while cyclosporine G or cyclosporine microemulsion was tried to reduce the toxic effects. Recently, CsA was reported to induce lipid peroxidation in renal cortical mitochondria, which may cause mitochondrial damage. To examine the hypothesis of lipid peroxidation in the pathogenesis of acute CsA induced nephrotoxicity, antioxidant vitamin E was co-administerated in the CsA induced acute nephrotoxicity. Sprague Dawley male rats weighing from 250 to 400 gm were heminephrectomized 7 days prior to the experiments. The rats were divided into 3 groups and each group consisted of 7 rats. In group I(control group), the rats were given sterilized olive oil intraperitoneally, in group II(CsA group), CsA 50 mg/kg of body weight/day intraperitoneally, and in group III(CsA with vitamin E), CsA 50 mg/kg of body weight/day intraperitoneally with vitamin E 10 mg/kg of body weight/day intramuscularly for 7 days respectively. From the 6th day, all experimental animals were placed in a metabolic cage collecting urine for the measurement of 24-hours urine thromboxane B2, the metabolite of thromboxane A2. On the 7th day, at the sacrifice of the experimental animals, blood samplings for the measurement of blood CsA level and serum creatinine and left nephrectomy for morphological study were performed. Comparison of mean serum creatinine levels between 2 study groups revealed 171.7+/-164.2 micro Mol/L in group II and 53.4+/-13.9 micro Mol/L in group III(p<0.05). Mean 24-hour urine thromboxane B2 levels were 39.0+/-6.9 ng/24 hours in group I, 74.8+/-22.6 ng/24 hours in group II, and 34.5+/-8.0 ng/24 hours in group III. Urine thromboxane B2 was significantly(p=.0026) lower in group III. The differences of morphological changes in group II and III can be summarized as a diminution of PAS(+) granules under the light microscope and a diminution of the numbers of secondary lysosomes in the proximal tubular epithelial cell under the electron microscope. In conclusion, this animal study provides an evidence that CsA-induced acute nephrotoxicity is related with lipid peroxidation and the antioxidant, vitamin E was considered to ameliorate CsA-induced acute nephrotoxicity in rats.
Animals ; Creatinine ; Cyclosporine* ; Epithelial Cells ; Humans ; Lipid Peroxidation ; Lysosomes ; Male ; Mitochondria ; Nephrectomy ; Olea ; Olive Oil ; Organ Transplantation ; Rats* ; Thromboxane A2 ; Thromboxane B2 ; Transplants ; Vitamin E* ; Vitamins*

In order to find out the relationship between arachidonic acid(AA) metabolites and the development of vasospasm following a subarachnoid hemorrhage(SAH), we evaluated the cerebrospinal fluid(CSF) levels of the two main AA metabolites, prostacyclin(PGI2) and thromboxane A2(TXAZ) by measuring their stable degredation products 6-keto-prostaglandin F1alpha(PGF1) and thromboxane B2(TXB2) using radioimmunoassay methods in 32 patients after an aneurysmal rupture and in 11 patients without an aneurysmal rupture as a control group. We compared the data between aneurysmal ruptured patients and control group patients. We also divided the data of the aneurysmal ruptured patients into 3 groups checking them between 1-4, 5-11, and 12-28 days after the SAH, and compared the data among the groups, then the data was also compared between non-vasospasm and clinical or severe angiographic vasospasm groups of patients. The results showed that the AA metabolism was enhanced after the SAH, The TXB2 increased the greatest amount in 1-4 days after the SAH and significantly decreased statistically 12 days after the SAH(p<0.002). This study also showed that the TXB2 level was significantly higher statistically in 1 to 4 days in the clinical or angiogrophically severe vasospasm group than in the non-vasospasm group of patients(p<0.032). PGF1 did not show any statistically significant changes according to the number of SAH days or a difference between the vasospasm and non-vasospasm groups. This result suggests if the AA metabolites are involved in the pathogenesis of cerebral vasospasm, and the lumbar CSF levels of AA metabolites in aneurysmal patients reflect the arterial synthesis of PGI2 and platelet origin of TXA2, the elevation of TXA2 or other vasoconstrictor prostaglandins is more likely to play a major role in the pathogenesis of vasospasm than PGI2 deficiency. The measurements of the CSF TXB2 in 1 to 4 days after a SAH may have an expectant value in the development of clinical or severe angiographic vasospasm(exclude the accompanying intraventricular hemorrhage patients).
Aneurysm* ; Arachidonic Acid ; Blood Platelets ; Cerebrospinal Fluid* ; Epoprostenol ; Hemorrhage ; Humans ; Metabolism ; Prostaglandins I ; Radioimmunoassay ; Rupture ; Subarachnoid Hemorrhage* ; Thromboxane A2 ; Thromboxane B2* ; Vasospasm, Intracranial