OBJECTIVETo investigate the effect of dietary saturated fat (SFA) from animal sources on the urine excretion 11-dehydro thromboxane B2 (TXB2) and 6-keto prostaglandin F 1alpha (PGF 1alpha) in 27 healthy free-living male subjects aged 30 to 55 years.

METHODSIt was a randomized crossover design. Each volunteer was randomly assigned to one of the two diets (high fat and low fat) for a period of 4 weeks, after which each subject resumed his usual diet for 2 weeks as a 'wash-out period', before being assigned to the other diet for an additional 4 weeks.

RESULTSSerum proportion of 20:4n-6 was 5% lower in the high fat (6.2% of total fatty acid) than in the low fat diet (6.5% of total fatty acid), which was associated with a significantly decreased ratio of the urinary excretion 11-dehydro TXB2 to 6-keto PGF 1alpha (P < 0.05). However, there was no significant fall in the absolute urinary excretion of 11-dehydro TXB2.

CONCLUSIONSDiet rich in SFA from animal sources may influence TXA2 formation via effect on tissue proportion of 20:4n-6.

6-Ketoprostaglandin F1 alpha ; urine ; Adult ; Arteriosclerosis ; physiopathology ; Cross-Over Studies ; Dietary Fats ; pharmacology ; Fatty Acids ; metabolism ; Humans ; Male ; Middle Aged ; Thrombosis ; physiopathology ; Thromboxane B2 ; analogs & derivatives ; urine

OBJECTIVETo explore the changes of the neurotransmitters in patients with chronic pulmonary heart disease (CPHD) and its clinical significance.

METHODSSeventy-two patients with CPHD (42 males, 30 females, mean age 55.6-/+8.9 years) were enrolled in the study, including 48 patients with compensated CPHD and 24 with uncompensated CPHD. Plasma endothelin (ET), thromboxance B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-K-PGFlalpha) were detected by radioimmunoassay. Thirty blood donors were selected as the normal control.

RESULTSCompared with the normal controls, CPHD patients showed abnormal pulmonary function, and significantly elevated levels of plasma ET and TXB2 (P<0.01) and lowered 6-K-PGFlalpha(P<0.01), but no significant differences were found between the patients with compensated CPHD and uncompensated CPHD (P>0.05). Plasma ET and TXB2 levels were inversely correlated to 6-K-PGFlalpha level (r=-0.4571, P<0.05).

CONCLUSIONThe patients with CPHD present with obvious changes of plasma ET, TXB2 and 6-K-PGFlalpha.

6-Ketoprostaglandin F1 alpha ; blood ; Adult ; Case-Control Studies ; Chronic Disease ; Endothelins ; blood ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Heart Disease ; blood ; Thromboxane B2 ; blood

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

OBJECTIVETo observe changes of thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha(6-Keto-PGF1 alpha) and TXB2/6-Keto-PGF1 alpha (T/P) in lungs of rats drowned in hypothermic sea water and to assess their influence on the blood-gas.

METHODSRats of different groups were drowned nearly to death in hypothermic sea water and then taken out of the water rapidly, observed at room temperature, after that the following steps were taken in 5, 15, 30, 60, 240 min and 360 min groups, that were 1 ml arterial blood taken from left heart for blood-gas analysis including pH, PaO2 and PaCO2, rectal temperature observed; at last, the ratio of left dry lungs with left wet lungs was assessed, TXB2 and 6-Keto-PGF1 alpha in right lungs were examined in all above groups and dead group(14 rats dead, only 4 examined).

RESULTSThe rectal temperature[(20.13 +/- 0.48) degree C], pH(6.68 +/- 0.03), PaO2[(45.00 +/- 6.30) mm Hg)], TXB2[(97.46 +/- 17.46) ng/L] and 6-Keto-PGF1 alpha[(25.59 +/- 8.12) ng/L] dropped to the lowest point in the 5 minutes group(P < 0.01), while PaCO2[(89.18 +/- 5.10) mm Hg] reached the highest point(P < 0.01), all above items from 5 minutes group then showed a recovering tendency, but only the pH in 240 minutes and 360 minutes groups as well as TXB2 in 360 minutes group and dead group reached near the level of normal control groups (P > 0.05); T/P had a rising tendency and reached the highest point in the 360 minutes group.

CONCLUSIONSThe production and secretion of TXB2 and 6-Keto-PGF1 alpha were influenced by hypothermia, hypoxemia and acidosis, the imbalance of T/P could be one of factors influencing the improvement of blood gas index.

6-Ketoprostaglandin F1 alpha ; analysis ; Animals ; Body Temperature ; Carbon Dioxide ; blood ; Drowning ; metabolism ; Hypothermia ; metabolism ; Lung ; chemistry ; Oxygen ; blood ; Rats ; Seawater ; Thromboxane B2 ; analysis

To evaluate the changes of 3', 5'-cyclic adenosine monophosphate (cAMP), thromboxane A2(TXA2) and prostacyclin (PGI2) in cerebrospinal fluid (CSF) in the asphyxiated newborn and explore their roles in hypoxic-ischemic brain damage (HIBD). Thirty-six full term newborns were divided into 3 groups, including 12 with moderate-severe hypoxic-ischaemic encephalopathy (HIE), 13 with mild HIE, 11 without HIE (control group). The levels of cAMP, TXB2 (TXA2 metabolite) and 6-keto-PGF1 alpha (PGI2 metabolite) in CSF and plasma were measured 36-72 h after birth by RIA, and the concentrations were expressed as nM/L (cAMP), ng/L(TXB2 and 6-keto-PGF1 alpha). The infants were followed-up at 6 and 12 month of age and Mental Development Index (MDI) and Psychomotor Development Index (PDI) were measured using Bayley Scales of Infant Development (BSID). The CSF cAMP level in moderate-severe HIE group was 8.60 +/- 2.40, significantly lower than that of the mild HIE group (14.83 +/- 2.84) and the control group (24.43 +/- 2.39) (for both P < 0.01). The levels of TXB2 and 6-keto-PGF1 alpha in CFS in the moderate-severe HIE group (206.06 +/- 29.74, 168.47 +/- 23.02, respectively) were significantly higher than in the mild HIE group (83.37 +/- 28.57, 131.42 +/- 16.57, respectively, P < 0.01) and the control group (41.77 +/- 21.58, 86.23 +/- 13.05, respectively, P < 0.01). The level changes of cAMP, TXB2 and 6-keto-PGF1 alpha in plasma in all groups were similar to those in CSF, but no significant difference was found between mild HIE group and the control group (P > 0.05). The follow-up results showed that MDI and PDI of the moderate-severe HIE group were the lowest (84.79 +/- 13.34, 83.50 +/- 13.28, respectively), followed by mild HIE group (102.19 +/- 7.02, 99.94 +/- 9.08, respectively), with the control group being the highest (116.63 +/- 12.08, 116.69 +/- 10.87, respectively). Univariate analysis showed some significant difference (the moderate-severe HIE group vs. the mild HIE group or the control group, P < 0.01; the mild HIE group vs. the control group P < 0.05). The results suggested that the concentration of cAMP, TXA2 and T/K ratio in CSF after neonatal asphyxia might be sensitive markers in evaluating the severity of brain damage in early stage and predicting the future outcome.
6-Ketoprostaglandin F1 alpha ; cerebrospinal fluid ; Asphyxia Neonatorum ; cerebrospinal fluid ; Biomarkers ; Cyclic AMP ; cerebrospinal fluid ; Epoprostenol ; cerebrospinal fluid ; Female ; Follow-Up Studies ; Humans ; Hypoxia-Ischemia, Brain ; cerebrospinal fluid ; Infant, Newborn ; Male ; Thromboxane A2 ; cerebrospinal fluid ; Thromboxane B2 ; cerebrospinal fluid

AIMTo study the effect of aspirin on chronic hypoxia and hypercapnic pulmonary hypertension.

METHODSSD rats were randomly divided into normal control group (A), hypoxic hypercapnic group (B), hypoxic hypercapnia + aspirin group (C). The concentration of TXB2 and 6-keto-PGF1alpha in plasma and in lung were detected by the technique of radioimmunology.

RESULTS(1) mPAP was significantly higher in B group than those of A and C group. Differences of mCAP were not significant in three groups. (2) Light microscopy showed that WA/TA (vessel wall area/total area) and PAMT (the thickness of medial smooth cell layer) were significantly higher in B group than those of A and C group. (3) The concentration of TXB2 and 6-keto-PGF1alpha in plasma and lung as well as the ratio of TXB2/6-keto-PGF1alpha were significantly higher in rats of B group than those of A and C group.

CONCLUSIONAspirin may inhibit hypoxic hypercapnia pulmonary hypertension and pulmonary vessel remodeling.

6-Ketoprostaglandin F1 alpha ; metabolism ; Animals ; Aspirin ; pharmacology ; Carotid Arteries ; pathology ; physiopathology ; Epoprostenol ; metabolism ; Hypercapnia ; physiopathology ; Hypertension, Pulmonary ; metabolism ; pathology ; physiopathology ; Hypoxia ; physiopathology ; Male ; Pulmonary Artery ; pathology ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Thromboxane A2 ; metabolism

AIMTo study the effect of 3,4-oxo-isopropylidene-shikimic acid (ISA) on H2O2 (200 mol.L-1, 4 h) injured human umbilical vein endothelial cells (HUVEC).

METHODSMorphological change was observed under microscop. Cell viability was assessed by MTT assay. The release of intracellular lactate dehydrogenase (LDH) and NO was assessed by colorimetry. Radioimmunoassay was used to assess 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha).

RESULTSPretreatment with ISA for 6 h alleviated the morphological damage of H2O2 induced HUVECs. At the concentration of 1-100 mumol.L-1, ISA prevented the inhibitory effect on cell viability induced by H2O2 in dose-dependent manner, but increased the ratio of cell viability from 60.4% to 84.3%. ISA reduced LDH release and increased the level of NO and 6-keto-PGF1 alpha in H2O2 induced HUVECs.

CONCLUSIONISA exerted protective effect on H2O2 injured HUVEC.

6-Ketoprostaglandin F1 alpha ; metabolism ; Cell Survival ; drug effects ; Cells, Cultured ; Endothelial Cells ; metabolism ; pathology ; Humans ; Hydrogen Peroxide ; antagonists & inhibitors ; Infant, Newborn ; L-Lactate Dehydrogenase ; metabolism ; Nitric Oxide ; metabolism ; Protective Agents ; pharmacology ; Shikimic Acid ; analogs & derivatives ; pharmacology ; Umbilical Veins ; cytology

BACKGROUNDCurrent prosthetic, small diameter vascular grafts showing poor long term patency rates have led to the pursuit of other biological materials. Biomaterials that successfully integrate into surrounding tissue should match not only the mechanical properties of tissues, but also topography. Polyglycolic acid (70/30) has been used as synthetic grafts to determine whether human vascular smooth muscle cells and endothelial cells attach, survive and secrete endothelin and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha).

METHODSEndothelial cells and smooth muscle cells were isolated from adult human great saphenous vein. They were seeded on polyglycolic acid scaffold in vitro separately to grow vascular patch (Groups A and B respectively) and cocultured in vitro to grow into vascular patch (Group C). Smooth muscle cells and endothelial cells were identified by immunohistochemical analysis and growth of cells on polyglycolic acid was investigated using scanning electron microscopy. The levels of endothelin and 6-keto-PGF1alpha in the culturing solutions were examined by radioimmunology to measure endothelial function.

RESULTSSeed smooth muscle cells adhered to polyglycolic acid scaffold and over 28 days grew in the interstices to form a uniform cell distribution throughout the scaffold. Then seed endothelial cells formed a complete endothelial layer on the smooth muscle cells. The levels of endothelin and 6-keto-prostaglandin F1 alpha in the culturing solution were (234 +/- 29) pg/ml and (428 +/- 98) pg/ml respectively in Group C and (196 +/- 30) pg/ml and (346 +/- 120) pg/ml in Group B; both significantly higher than in Groups A and D (blank control group, all P < 0.05).

CONCLUSIONSCells could be grown successfully on polyglycolic acid and retain functions of secretion. Our next step is to use human saphenous vein smooth muscle cells and endothelial cells to grow tubular vascular grafts in vitro.

6-Ketoprostaglandin F1 alpha ; analysis ; Adult ; Blood Vessel Prosthesis ; Coculture Techniques ; Endothelial Cells ; physiology ; Humans ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; physiology ; Polyglycolic Acid ; pharmacology ; Saphenous Vein ; cytology ; Tissue Engineering

BACKGROUNDHypertensive crisis could be found after operation in patients with hypertensive intracerebral hemorrhage (HICH). The aim of this study was to explore the changes and the roles of some vasoactive polypeptides during postoperative hypertensive crisis in patients with HICH.

METHODSA total of 31 patients, who were admitted for craniotomy, were enrolled into this study. After the operation, the patients were divided into three groups. Group I consisted of 9 patients with postoperative hypertensive crisis, and group II was composed of 13 patients without postoperative hypertensive crisis. Nine patients, who denied history of hypertension or HICH, were set as group III. The levels of some vasoactivators in the three groups were measured before and after the operation. The differences in the results among the groups were analyzed using the ANOVA. The data collected before and after the operation in the group I was compared by Wilcoxon test.

RESULTSThe concentration of endothelin in group I was significantly higher than that in group III (P < 0.05). The level of thromboxane A2 and the ratio of thromboxane B2 to 6-keto-PGF1a in group I were significantly higher than those in the other two groups (P < 0.05). In group I, the levels of plasma renin activity, angiotensin II, aldosterone, catecholamine, and endothelin before the operation were significantly higher than those determined after the operation (P > 0.05).

CONCLUSIONSPostoperative hypertensive crisis may be due to the increased thromboxane A2 and relatively inadequate prostacyclin, especially 6-keto-PGF1a. The increased level of endothelin and intraoperative stimulation also play a certain role in the development of postoperative hypertensive crisis.

6-Ketoprostaglandin F1 alpha ; blood ; Adult ; Aged ; Endothelins ; blood ; Female ; Humans ; Hypertension ; blood ; etiology ; Intracranial Hemorrhage, Hypertensive ; blood ; physiopathology ; surgery ; Male ; Middle Aged ; Postoperative Complications ; blood ; Thromboxane B2 ; blood

AIMTo study the effect of Safflower injection (a compound of Chinese Traditional medicine) on pulmonary hypertension in rat during chronic hypoxia and hypercapnia.

METHODSSprague-Dawley rats were randomly divided into normal control group (A), hypoxic hypercapnic group (B), hypoxic hypercapnia + Safflower injection group (C). The concentration of TXB2 and 6-keto-PGF18 in plasma and in lung homogenate were detected by the radioimmunoassay.

RESULTS(1) mPAP, weight ratio of right ventricle (RV) to left ventricle plus septum (LV + S) were much higher in rats of hypoxic hypercapnic group than those of control group. Differences of mCAP among the three groups were not significant. (2) The concentration of TXB2 and the ratio of TXB2/6-keto-PGF1a were significantly higher in rats of B group than those of A and C group. (3) The results examined by light microscopy showed that WA/TA (vessel wall area/total area), SMC (the density of medial smooth muscle cell) and PAMT (the thickness of medial smooth cell layer) were significantly higher in rats of B group than those of A and C group. (4) The results examined by electron microscopy showed proliferation of medial smooth muscle cells and collagen fibers of pulmonary arterioles in rats of B group, and Safflower injection could reverse the changes mentioned above.

CONCLUSIONSafflower injection may inhibit hypoxic hypercapnia pulmonary hypertension and pulmonary vessel remodeling by decreasing the ratio of TXB2/6-keto-PGF1a.

6-Ketoprostaglandin F1 alpha ; metabolism ; Animals ; Carthamus tinctorius ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Hypercapnia ; metabolism ; pathology ; physiopathology ; Hypertension, Pulmonary ; prevention & control ; Hypoxia ; metabolism ; pathology ; physiopathology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Thromboxane B2 ; metabolism