Ratio Of TXB2 Research Articles

Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy.

BackgroundPregnancy increases the risk of morbidity and mortality in sickle cell disease. We previously showed pregnant women with sickle cell disease to have a relatively low plasma renin concentration in late pregnancy, associated with a lack of the expected plasma volume expansion. We hypothesized this to be due to increased systemic vascular resistance through an imbalance between the vasodilator prostacyclin and vasoconstrictor thromboxane, associated with decreased glomerular filtration rate (GFR).ObjectiveTo compare estimated prostacyclin, thromboxane and GFR in non-pregnant and pregnant women with hemoglobin SS (HbSS) and AA (HbAA).Study designFour groups of 20 normotensive, nulliparous women were studied in Lagos, Nigeria: pregnant HbSS or HbAA women at 36–40 weeks gestation; non-pregnant HbSS and HbAA controls. We measured stable metabolites of prostacyclin and thromboxane A2 by enzyme-linked immunosorbent assay; GFR using the Cockcroft-Gault equation. Data analysis was by independent (Student’s) t-test or Mann-Whitney U test for comparisons between any two groups of continuous variables, univariate ANOVA for multiple groups and Pearson’s correlation coefficient for degree of association between variables.ResultsHbSS women had lower serum 6-keto-PGF1α concentrations than HbAA, whether pregnant or non-pregnant (P<0.001; P<0.004 respectively). Conversely, pregnant HbSS women had higher serum TxB2 (P<0.001); non-pregnant HbSS women had non-significantly higher TxB2 concentrations. The 6-keto-PGF1α:TxB2 ratio was markedly increased (pro-vasodilatory) in HbAA pregnancy (P<0.001) but reduced in HbSS pregnancy (P = 0.037). GFRs (mL/min) were higher in non-pregnant HbSS than HbAA (P<0.008) but only marginally raised in HbSS women in late pregnancy (P = 0.019) while markedly raised in HbAA pregnancy (P<0.001).ConclusionThe lower ratio of prostacyclin-thromboxane metabolites in HbSS pregnancy may indicate endothelial damage and an increased tendency to vasoconstriction and clotting. If confirmed by subsequent longitudinal studies, interventions to increase prostacyclin and reduce thromboxane, such as low dose aspirin, may be potentially useful in their management.

Existence of Compensatory Defense Mechanisms Against Oxidative Stress and Hypertension in Preeclampsia

Objective: Preeclampsia is a complex obstetrical syndrome characterized by hypertension and proteinuria. This syndrome is associated with oxidative stress, antioxidant imbalance and impaired production of vasoactive eicosanoids such as thromboxane A2 (TXA2), a potent vasoconstrictor, and prostacyclin (PGI2), a well-known vasodilator. We hypothesized that there was a relationship between antioxidant vitamins, such as vitamin E and coenzyme Q10 (CoQ10), and the production of vasoactive eicosanoids— PGI2 and TXA2—potentially regulated by pro-oxidants and antioxidants in preeclampsia. Methods: Therefore, the plasma levels of vitamin E, CoQ10, TXA2 and PGI2 in normotensive (n = 30) and preeclamptic (n = 29) pregnancies were evaluated. Reduced and oxidized forms of vitamin E and CoQ10 in blood were measured using a HPLC coupled to electrochemical detection. The levels of TXB2 and 6-keto-PGF1α, stable metabolites of TXA2 and PGI2 respectively, were measured by ELISA. Results: The CoQ10 oxidized/reduced ratio was significantly higher in preeclamptic compared to normotensive pregnancies (p = 0.04). A strong correlation between plasma levels of reduced vitamin E and CoQ10, corrected for apolipoprotein B, was observed only in preeclampsia (r = 0.69, p < 0.0001). The 6-keto-PGF1α/TXB2 ratio was higher in preeclampsia than in controls (p = 0.02), and this ratio was correlated to the oxidized/reduced ratio of both, vitamin E and CoQ10 in all pregnancies (p <0.023). Conclusion: The data indicated that CoQ10 is a sensitive marker of oxidative stress in preeclampsia. The correlation between vitamin E and CoQ10 suggested a coordinated defense mechanism against oxidation. Furthermore, the higher 6-keto-PGF1α/TXB2 ratio that strongly correlated with oxidative stress markers, suggests a mechanism developed by the maternal cardiovascular system to counteract hypertension during preeclampsia.

Changes of TXA2 and PGI2 during postoperative hypertensive crisis in patients with hypertensive intracerebral hemorrhage

In order to explore the changes and the roles of TXA2 and PGI2 during postoperative hypertensive crisis in patients with hypertensive intracerebral hemorrhage, 31 cases subject to craniotomy were divided into three groups: group A, 9 patients with postoperative hypertensive crisis; group B, 13 patients without postoperative hypertensive crisis; and group C, 9 patients without history of hypertension and hypertensive intracerebral hemorrhage. TXA2, TXB2, 6-keto-PGF1 alpha and PGI2 were measured after operation in the three groups respectively. The postoperative blood pressure in group A, including SBP and DBP, was elevated more obviously than that in the other two groups. TXA2 and PGI2 in group A were significantly higher than those in other two groups (P<0.01). Moreover, the ratio of TXB2 to 6-keto-PGF1 alpha in group A was significantly higher than that in other two groups (P<0.05). The increase of TXA2 and the relative inadequacy of prostacyclin, especially 6-keto-PGF1 alpha, may play roles in the postoperative hypertensive crisis. And the increased value of TXB2 to 6-keto-PGF1 alpha could provide the basis for diagnosis of postoperative hypertensive crisis.

Effect of ginseng and prepared aconite injection on TXA2/PGI2 and nuclear factor-κB in rat model of hepatic ischemia-reperfusion

AIM: To explore the protective effects of ginseng and prepared aconite (Shen Fu) injection on the TXA2/PGI2 and nucleus factorκB (NF-κB) in a rat model of hepatic ischemia-reperfusion (IR). METHODS: Twenty-four male Wistar rats weighing 200-250g were randomly divided into Shen Fu (SF) group treated with intraperitoneal SF injection (10 mL/kg) and IR group treated with 0.9% sodium chloride solution (10 mL/kg) as control group. Hepatic ischemia was induced by Pringle s maneuver for 15 minutes, and then reperfusion was performed for one or three hours. Venous blood samples were collected three hours after reperfusion for measurement of TXB2 and 6-keto-PGF(subscript 1α). Liver tissue samples were collected one or three hours after reperfusion, for measurement of deoxidized glutathione (GSH) and morphological and immunochemical studies. RESULTS: Plasma TXB2 was lower in the SF group than in the JR group after three-hour reperfusion (118.7±19.1 vs 386.3±282.7, P＞0.05), while 6-keto-PGF(subscript 1α) was higher in the SF group than in the IR group (1081.7±282.7 vs 960.0±209.9, P＞0.05). The ratio of TXB2 and 6-keto-PGF(subscript 1α) (0.11±0.03 vs 0.39±0.24, P＜0.05) was significantly lower in the SF group. Fifteen minutes after ischemia and one hour after reperfusion, NF-κB p65 was expressed in hepatocytes and Kuffer cells. The percentage of NF-κB p65 positive cells in the SF group was significantly lower (59.33%±11.06% vs 75.83%±11.46%, P＜0.05) and GSH was slightly higher (47.59±19.07 vs 37.32±4.71, P＞0.05) than those in the IR group. Three-hour reperfusion fifteen minutes after ischemia caused important histologic alterations in the liver. Marked structural abnormalities were observed in the IR group, such as massive hepatocyte swelling, necrosis, mitochondria edema and vacuolar changes. In the SF group, hepatic tissue injury was significantly improved. CONCLUSION: Shen Fu injection protects hepatic tissue from ischemia-reperfusion injury by decreasing the ratio of thromboxane A2 and prostacyclin and inhibiting the activation of NF-κB.

Study on therapeutic mechanism of Neiyifang in treating endometriosis

Objective: To observe the clinical effect of Neiyifang (NYF) in treating endometriosis and to explore its therapeutic mechanism through observing its influence on plasma β-endorphin (β-EP) in different menstrual stages and levels of prostaglandins (PGs) in menstruation.Methods:NYF was administered to 104 patients with endometriosis one dose daily with 3 successive menstrual cycles as one therapeutic course. Peripheral blood β-EP level in follicular, luteal and menstrual stages, as well as PGF2α, PGE2, thromboxane B2 and 6-keto-PGFl α levels in menstrual stage were detected by RIA, and controlled with those in 15 healthy persons.Results: (1) The total effective rate of NYF was 81.3% and it showed significant effect in improving patients’ clinical symptoms and physical signs; (2) In menstrual stage, the levels of β-EP, 6-keto-PGFα/ TXB2 were lower(P <0.05) and levels of PGF2α, PGE2, TXB2 and 6-keto-PGF1α were higher (P< 0. 05) in patients than those in control, and the higher the level of PGE2, the severer the menalgia, (3) NYF could increase levels of β-EP, 6-keto-PGF1α, and reduce levels of PGF2α, PGE2α in menstrual stage of patients (all P<0.05).Conclusion: (1) NYF has good clinical effect in treating endometriosis; (2) Patients’ symptom of menalgia is closely related with the excessive high levels of PGF2α and PGE2, PGI2/TXA2 ratio disturbance, and excessive low level of β-EP; (3) NYF could significantly decrease the PGE2, PGF1α levels, increase the 6-keto-PGF1α/TXB2 ratio and the level of β-EP, so as to alleviate the menalgia in patients with endometriosis.

Effect of Acute Thromboxane A2 Inhibition on the Renal Hemodynamics in a Spontaneously Non–Insulin-Dependent Diabetic Rat, Otsuka Long-Evans Tokushima Fatty Rat

Thromboxane (TX) A2 plays important roles on renal injuries in streptozotocin (STZ)-induced diabetic rats, whereas its role on the renal injuries in non–insulin-dependent diabetic (NIDDM) rats remains unknown. We evaluated the effects of an intravenous infusion of TXA2 synthetase inhibitor (OKY-046, 6 mg/kg/h) on the clearances on inulin and para-aminohippurate (Cin, CPAH) in a spontaneously NIDDM rats, Otsuka Long-Evans Tokushima Fatty (OLETF) rats n = 8 , and Long-Evans Tokushima Otsuka (LETO) rats n = 7 , served as control rats, at the age of 40–44 weeks. OLETF rats showed obesity, moderate hyperglycemia, and hyperinsulinemia. Urinary excretion of TXB2 was slightly higher and the ratio of TXB2 to 6-keto prostaglandin F1α (6-kPG) was significantly higher in OLETF rats (TXB2/6-kPG: 0.22 ± 0.04 versus 0.12 ± 0.02, P < 0.05). Both Cin and CPAH were significantly higher in OLETF rats than in LETO rats (Cin: 1.1 ± 0.1 versus 0.7 ± 0.1 mL/min/100 g BW, CPAH: 3.1 ± 0.2 versus 2.3 ± 0.3 mL/min/100gBW, P < 0.01). OKY-046 did not restore Cin and CPAH in OLETF rats although it significantly decreased urinary excretion of TXB2, and thus ameliorated TXB2/6-kPG in OLETF rats. These data suggested that TXA2 was not involved in the renal hyperfiltration in OLETF rats at the age of 40–44 weeks, and that TXA2 might contribute to renal injuries in OLETF rats through mechanisms other than hemodynamic injury.

Glioma prostaglandin levels correlate with brain edema.

The present study was designed to prospectively investigated the prostaglandin (PG) levels and extent of peritumoral edema in 30 cases of glioma by using methods of radioimmunoassay and imaging. Both TXB2 and 6-keto-PGF1 alpha levels in all glioma groups went up over that in the control group. TXB2 level and ratio of TXB2/6-keto-PGF1 alpha were markedly increased with the extent of tumor malignancy. Water concentration in anaplastic astrocytoma and glioblastoma were significantly elevated. Difference in TXB2 level and TXB2/6-keto-PGF1 alpha ratio among three edema grades were statistically significant. TXB2 level and ratio of TXB2/6-keto-PGF1 alpha were closely correlated with water concentration (r1 = 0.53, r2 = 0.72, P < 0.01). Our findings suggested that the metabolism of PG in glioma were in the state of disorder, and that the imbalance between PGI2 and TXA2 may be one of factors which affect the formation of peritumoral edema.

Simultaneous Quantitative Analysis of Prostaglandins and Thromboxane after Low-Dose X Irradiation

The appearance of prostaglandins and thromboxane in mouse serum after X irradiation was observed by simultaneous quantitative analysis using gas chromatography/mass spectrometry/selected ion monitoring with stable isotope dilution methods. Mice of two strains (C57BL/CN Jcl and BALB/c) showed similar responses to X irradiation. In C57BL/6N Jcl mice, 0.2 Gy irradiation elicited a significant increase in generation of prostanoids: Immediately after irradiation, the 6-keto PGF1 alpha:TXB2 ratio and the level of PGE2 increased, after 20 min 6-keto PGF1 alpha and PGE2 increased, and after 4 h PGE1 and PGE2 increased. In BALB/c mice, generation of prostanoids was increased significantly immediately after irradiation (6-keto PGF1 alpha, 6-keto PGF1 alpha:TXB2 ratio, PGE2), and the increase was maintained from 20 min to 4 h (PGE1, PGE2) after 0.2 Gy irradiation. In C57BL/6N Jcl mice, a significant increase in production of 9alpha,11beta-PGF2 was observed at 20 min after irradiation. In BALB/c mice, a significant increase in 9alpha,11beta-PGF2 was seen immediately after irradiation and was maintained for 20 min. In C57BL/6N Jcl mice, the level of 8-epi PGF2 alpha was clearly increased 4 h after 4 Gy irradiation. A slight and slow increase was also seen after 0.2 Gy irradiation. In BALB/c mice, 8-epi PGF2 alpha was increased significantly at 20 min and 4 h after 4 Gy irradiation. These results show that 0.2 Gy irradiation stimulates production of prostanoids related to the inflammatory response in mice.

Sickle cell vaso-occlusive crisis is associated with abnormalities in the ratio of vasoconstrictor to vasodilator prostanoids.

Plasma levels of 6-keto-prostaglandin F1 alpha (6kPGF1 alpha) and thromboxane (Tx) B2 have been assessed in sickle cell disease (SCD) with discrepant results. Inasmuch as direct measurement of plasma prostanoids is fraught with the problem of interfering substances, we assessed plasma 6kPGF1 alpha and TxB2 levels in patients with SCD by RIA after extraction of eicosanoids and separation by HPLC. We demonstrate that the 6kPGF1 alpha and TxB2 levels in children with SCD in steady state as well as in vaso-occlusive crisis (VOC) are significantly lower when compared with those from age-matched controls. The VOC plasma 6kPGF1 alpha and TxB2 levels were, however, significantly elevated when compared with those from children in steady state. Changes similar to those noted with unpaired plasma samples were also observed when paired steady state and VOC plasmas from the same patients were assessed. The ratio of TxB2 to 6kPGF1 alpha was, however, significantly elevated in patients with SCD in crisis when compared with eicosanoid ratios obtained during steady state. In an attempt to understand whether the abnormality in 6kPGF1 alpha was due to an impairment in endothelial cell prostacyclin-regenerating ability, we compared the ability of plasma from controls and children with SCD to activate arachidonic acid (AA) release and prostacyclin production by [14C]AA-prelabeled bovine aortic endothelial cells. Our results suggest that the decreased 6kPGF1 alpha levels in plasma from children with SCD was not due to an effect on substrate AA release but rather a modulatory effect of sickle plasma components on endothelial cell cyclooxygenase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of endotoxin on hypoxic pulmonary vasoconstriction--the role of prostaglandins and leukotrienes.

In this study, we observed the effect of endotoxemia on hypoxic pulmonary vasoconstriction (HPV) in dogs and explored roles played by prostaglandins and leukotrienes in this process. 5 micrograms/kg BW of E. coli endotoxin induced transient rise in pulmonary arterial pressure and pulmonary vascular resistance (PVR). 30 min after injection of endotoxin when PVR tended to decline, pulmonary vasoconstriction response to alveolar hypoxia was lost, and the ratio of TXB2 to 6-keto-PGF1 alpha decreased significantly. HPV was enhanced at 60-100 min and then returned to the control level at 2 h after injection of endotoxin. At these periods the ratio of TXB2 to 6-keto-PGF1 alpha was the same as before use of endotoxin, whereas plasma concentration of leukotrienes was markedly increased. Indomethacin could prevent the early loss of HPV, but no effect on the late increment of HPV was found. Diethylcarbamazine, which blocked the production of leukotrienes after use of endotoxin, could inhibit late increment of HPV. We concluded that the early loss of HPV was related to the vasodilator prostacyclin, and the late increment of HPV was mainly brought about by leukotrienes.

Eicosanoid Production in the Caudate Nucleus and Dorsal Hippocampus after Forebrain Ischemia: A Microdialysis Study

Thromboxane (Tx)B2 and 6-keto-prostaglandin (6-keto-PG) F1 alpha formation in the hippocampus and caudate nucleus were evaluated by microdialysis during and following forebrain ischemia. Spontaneously hypertensive rats were subjected to bilateral carotid artery occlusion with simultaneous hypotension for 8, 14, or 20 min. Dialysate was collected during the ischemic interval and during the reperfusion period. TxB2 and 6-keto-PGF1 alpha levels were measured by radioimmunoassay. In both structures, TxB2 production increased significantly during the reperfusion period in all three ischemic groups. By contrast, increased 6-keto-PGF1 alpha elaboration was observed after only the longest ischemic duration. While TxB2 levels gradually decreased during the 3-h reperfusion period in all groups, the levels in the group subjected to 8 min of ischemia returned to control values most rapidly. A relationship between the duration of ischemia and TxB2 production was therefore evident. 6-Keto-PGF1 alpha levels increased in only the group subjected to 20 min of ischemia and, by contrast to the pattern of TxB2 change, 6-keto-PGF1 alpha levels remained elevated throughout the reperfusion period. During reperfusion, the ratio of TxB2 to 6-keto-PGF1 alpha increased substantially versus the preischemic period in both structures. The data demonstrate that eicosanoid elaboration following cerebral ischemia can be evaluated by the microdialysis technique. In addition, they indicate that the thresholds (duration of ischemia) for the postischemic production and the temporal profiles of TxB2 and 6-keto-PGF1 alpha in the caudate and hippocampus differ. They also demonstrate that there is regional heterogeneity in the patterns of eicosanoid elaboration after forebrain ischemia.

REGIONAL RECOVERY OF EICOSANOIDS AFTER FOREBRAIN ISCHEMIA BY MICRODIALYSIS IN RATS

The production of prostaglandins in the post-ischemic brain may affect the evolution of ischemic neuronal injury. In particular, it has been suggested that the relative balance between prostaglandins with opposing effects on the vasculature might influence post-ischemic cerebral perfusion, and thereby alter the the extent of neuronal injury1,2. An exacerbation of neuronal injury would be predicted if prostanoids with vasoconstrictive properties are produced in excess of those that produce vasodilatation. A recent investigation in our laboratory had demonstrated that thromboxane B2 (a stable metabolite of thromboxane A2) was produced in greater quantities than 6-keto-prostaglandin PGF1a (a stable metabolite of prostacyclin) in both the caudate nucleus (CN) and dorsal hippocampus (HPC) in the rat3. However, the ratio of TxB2 to 6-keto-PGF1a was substantially greater in the CN. Therefore, a greater susceptibility of the CN to ischemic damage would be predicted. This is not thought to be the case, and accordingly, additional factors must also playa role. These factors might include the production of other eicosanoids with vasoactive effects.

Compound polyglactin 910/polypropylene small vessel prostheses

This study evaluated morphologic and functional characteristics of tissue reactions to compound prostheses of 69% absorbable polyglactin 910 (PG910) and 31% nonabsorbable polypropylene in the rabbit. Forty-two woven PG910/polypropylene prostheses (24 × 4 mm internal diameter) implanted into rabbit infrarenal aortas were harvested after 2 weeks to 12 months. Each explant was photographed and sectioned for light microscopy and transmission and scanning electron microscopy. Randomly selected explants underwent either compliance and bursting strength measurements or assays of production of prostacyclin and thromboxane metabolites by luminal surfaces of both regenerated conduits and normal control aortas in response to administered sodium arachidonate. Results showed 100% patency with no aneurysms and 2% stenoses (1 of 42 prostheses). Confluent endothelial-like cellular luminal surfaces covering oriented smooth muscle—like myofibroblasts comprised the inner capsules whose thicknesses stabilized at 1 to 2 months. Only residual polypropylene remained in the prostheses after 2 months. Compliance studies reflected a 0.65 mm (14%) change over a pressure range of 0 to 160 mm Hg. All regenerated prosthesis-tissue complexes had bursting strengths greater than the proximal perianastomotic native aortas, which burst between 600 and 2000 mm Hg. At 1 month the rate of production of 6-keto-PGF1α per square millimeter of surface area of experimental segments was normal. Production of 6-keto-PGF1α by experimental segments at 3 months had increased fourfold whereas thromboxane B2, (TxB2) production remained unchanged. The 6-keto-PGF1α/TxB2 ratio increased from 1 to 4 months. This study demonstrates clinically efficacious morphologic, mechanical, and biochemical characteristics of PG910/polypropylene-elicited vascular prosthesis-tissue complexes.

S-4-6 Effect of Glibornuride on blood viscosity, platelet aggregation, TXB2, PGI2 and the ratio of TXB2 to PGI2 in NIDDM

S-4-6 Effect of Glibornuride on blood viscosity, platelet aggregation, TXB2, PGI2 and the ratio of TXB2 to PGI2 in NIDDM

Effect of glibornuride on blood viscosity, platelet aggregation, TXB2, PGI2 and the ratio of TXB2 to PGI2 in NIDDM

Effect of glibornuride on blood viscosity, platelet aggregation, TXB2, PGI2 and the ratio of TXB2 to PGI2 in NIDDM

Increased release of prostaglandins from the mesenteric vascular bed of diabetic animals: The effects of glucose and insulin

To study prostaglandin (PG) metabolism in peripheral vascular beds, PGs and TxB2 released from perfused mesenteric tissues were measured in both normal and streptozotocin (STZ)-induced diabetic rats. The release of 6-keto-prostaglandin F1α (6-keto-PGF1α), thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) was significantly increased in mesenteric vascular beds from diabetics in comparison with control rats. The 6-keto-PGF1α/TxB2 ratio was decreased in diabetics. In order to clarify the mechanism of this imbalanced synthesis of eicosanoids, we infused buffer with 500 mg/dl glucose which was similar to the concentration of blood glucose in the diabetic rats. In response to this high glucose concentration, TxB2 released into the effluent from the mesenteric beds of normal animals was increased to the diabetic level. The release of the other PGs was not changed significantly. The 6-keto-PGF1α/TXB2 ratio was decreased in control rats perfused with buffer containing 500 mg/dl glucose. We also investigated the effect of insulin (50 and 100 μU/ml) in the diabetic mesenteric vascular beds, but there were no changes in prostaglandin or TxB2 release. These data suggest that a high glucose level may have an important role in regulating TxA2 synthesis and in modulating the balance between PGI2 and TxA2 in diabetes. It is postulated that an increase in the micro-circulation of PGI2 may partially be protective against the progression of angiopathy.

1640 PROSTACYCLIN DEFICIENCY DOES NOT PLAY A PIVOTAL ROLE IN HEMOLYTIC UREMIC SYNDROME (HUS)

A decrease in the prostacyclin (PGI2) stimulating activity of plasma has been reported in children with HUS. Although no study has attempted to assess plasma PGI2 levels themselves, the presence of a decrease in the PGI2 stimulating activity has been equated with a deficiency of PGI2 in HUS. We have conducted an evaluation of plasma prostanoids (PGI2 and TXB2) in 5 children admitted to SUNY during an epidemic of HUS in the northeast and in 23 controls. We were unable to document a pivotal role for PGI2 deficiency in HUS. Using an RIA for plasma 6KPGF1α(the stable hydrolysis product of PGI2), patients with HUS demonstrated elevated 6KPGF1α levels of 1.05±0.3 (1SD) pmol/ml when compared to controls (0.41±0.13; p<0.001). Increased production of PGI2 in HUS was accompanied by a concomitant increase in plasma thromboxane. Compared to a plasma TXB2 level of 0.10±0.06 in controls, the mean level in patients with HUS was 0.33±0.09pmol/ml (p<0.001). When the ratio of plasma TXB2 to 6KPGF1α was evaluated as an index of proaggregatory and vasoconstrictor versus antiaggregatory and vasodilator influences, no difference was observed between controls (0.33±0.06) and HUS (0.33±0.08). Changes in prostanoid production in HUS appear to reflect vascular injury (T6KPGF1α) and concomitant platelet consumption (↑TXB2). A deficiency of PGI2 in HUS was an attractive hypothesis that explained the systemic hypertension and the observed thrombocytopenia. Our finding however does not support a role for prostacyclin deficiency, and underscores the heterogenousness of HUS.

1691 ASSOCIATION OF CEREBRAL PROSTAGLANDIN IMBALANCE WITH PERINMAL STROKE

Asphyxia, with its attendant hypotension, is the most common cause for neonatal cerebral infarction. We have demonstrated uncoupling of cerebral blood flow & metabolism in a hemorrhagic hypotension(HH) model for cerebral infarction in the newborn beagle pup. We report the effects of HH on regional cerebral prostaglandin (PG) levels in newborn beagle pups exposed to a similar insult. Pups were randomized to (HH) or no insult (C). HH was induced by slow venous hemorrhage to maintain MABP 20-30 mm Hg. Fifteen minutes following HH/C, the animals underwent in vivo freezing of brain. PG determinations for 6-keto PGF1α, the stable metabolite of PGI2, TXB2, the stable breakdown product of TXA2, & PGE2 were performed using radioimmunoassays. MABP of HH group was 74 prior to & 26 mm Hg following insult; the MABP of the C group remained 71 mm Hg. The PG levels & ratios of 6-ketoPGF1α/TXB2(ratio) were as follows: The alterations in the cerebral PGI2/TXA2 balance may in part be responsible for the changes found in cerebral blood flow & metabolism & the neuropathological consequences of perinatal ischemia.

Type IIa高脂質血症における血小板リン脂質構成脂肪酸比と血中Prostanoidsの動向ならびにクリノフィブレート投与の影響

It has been reported that patient with Type IIa Hyperlipidemia which results in metabolic abnormarities of serum Prostanoids are prone to have Arteriosclerosis.Tremori et al reported a positive correlation between serum Cholesterol levels and plasma Thromboxane B2 levels. Serum Cholesterol levels have a close relationship to prostaglandin metabolism in platelets. In the case of Type ha Hyperlipidemia, we have found both platelet aggregation and Thromboxane B2 levels to be significantly elevated compared to controls.In addition, the ratio of C20: 4of phospholipid, P. E., P. C. and NEFA in platelets were significantly elevated in Type IIa Hyperlipidemia. This implies that abnormalities of Cholesterol metabolism affect C20: 4levels in platelets, and therefore the process of prostaglandin metabolism.After administering Clinofibrate, a lipid lowering agent, to patients with Type ha Hyperlipidemia, there was a significant improvement of the ratio of TX B2 to 6-Keto-PGF1α, a significant reduction in TX B2, platelets aggregation and C20: 4 levels of P. E. in platelets phospholipids, consistent with a decrease in serum Cholesterol. We conclude these strongly suggest the relation of occurance of thrombosis and abnormalities of serum lipid through Prostanoids metabolism.

虚血性心疾患ならびに脳梗塞における Aspirin 投与法の検討

Thirteen patients with arteriosclerotic diseases and 5 normal healthy subjects were orally given 300mg aspirin once daily for 4 consecutive weeks. Examinations with a stress on platelet functions were carried out before and after the first administration and during at the end of 4 weeks of treatment to clarify the influence of aspirin on them. The following results were obtained:1) The serum lipid (total cholesterol, triglycerides and HDL-cholesterol) levels and the atherogenic index were not significantly different before and after the consecutive daily administration of aspirin in both groups.2) The proportion of arachidonic acid (C: 20:4) to the phospholipid (PE and PC) levels and NEFA in plasma and platelet produced no significant changes before and after the consecutive daily administration of aspirin.3) The platelet aggregation tended to return to the pretreatment level 24 hours after the first administration in the group of normal healthy subjects, but this tendency was not clear in the group of patients with arteriosclerosis. In addition, the 24 hour values during the consecutive daily administration showed a similar tendency.4) With regard to the influence on prostanoids, the ratio of TXB2 to 6-Keto-PGF1α decreased after the first administration, but it showed little alternation throughout the day and was maintained at a lower level constantly during the consecutive daily administration in both groups. When the range of fluctuation was examined by defining the pretreatment value as 100%, TXB2 was primarily suppressed in both groups. The reduction of the ratio seemed to be mainly due to this change. Moreover, 6-Keto-PGF1α tended to be decreased to a less degree and TXB2 to a higher degree in the group of patients with arteriosclerosis than in that of normal healthy subjects.5) The βTG and PF-4 levels were significantly decreased as compared with the pretreatment values, in the arteriosclerosis group but no significant changes in these parameters were observed in normal healthy subjects.6) There was no significant correlation between the serum aspirin concentration and platelet functions.The results indicate that aspirin exerts a satisfactory effect as an antiplatelet drug when administered at 300mg once daily and additionally that its suppressive potency is within a constant limit. Thus, continuous long-term administration of aspirin is suggested to be possible.