Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the cause of low prostacyclin (PGI2) production in severe preeclampsia (PE), we studied the activities of phospholipase A2, cyclooxygenase, and PGI2 synthase in umbilical venous endothelial cells obtained from healthy pregnant women and from patients with mild or severe PE. Umbilical venous endothelial cells homogenized in a buffer solution were analysed by calculating the apparent Vmax (mean +/- SEM: p mol/min mg protein) and Km (mean +/- SEM: microM) values for phospholipase A2 activity by the release of arachidonic acid from phosphatidylcholine, for the activity of a complex of cyclooxygenase and PGI2 synthase by the conversion of arachidonic acid to PGI2, and the activity of PGI2 synthase by conversion of PGH2 to PGI2. The phospholipase A2 activity of normal-pregnancy cells (Vmax: 17.0 +/- 2.7 Km: 0.26 +/- 0.04) (n = 10) significantly exceeded that of cells from women with either mild PE (5.8 +/- 0.5, 0.12 +/- 0.02) (n = 4) or severe PE (6.3 +/- 2.0, 0.08 +/- 0.03) (n = 5). The apparent combined activity of cyclooxygenase and PGI2 synthase in mild PE (552 +/- 142, 0.29 +/- 0.07) (n = 8) significantly exceeded that of a normal pregnancy (176 +/- 42, 0.76 +/- 0.25) (n = 7), whereas that in severe PE (326 +/- 36, 3.26 +/- 0.78) (n = 3) was significantly lower than that of a normal pregnancy. PGI2 synthase activity in mild PE (305 +/- 50, 0.12 +/- 0.07) (n = 4) exceeded that of a normal pregnancy (220 +/- 45, 0.13 +/- 0.06) (n = 5), whereas that in severe PE (55 +/- 12, 0.16 +/- 0.04) (n = 3) was lower than that of a normal pregnancy. The phospholipase A2 activity in cells of normal pregnant women exceeded that of cells of women with mild or severe PE. The combined activity of cyclooxygenase and PGI2 synthase in a normal pregnancy was lower than in mild PE, but higher than in severe PE. Similar results were found for PGI2 synthase activity; in normal pregnancy the activity was less than in mild PE, but higher than in severe PE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activities of phospholipase A2, cyclooxygenase, and PGI2 synthase of umbilical venous endothelial cells in preeclamptic women. 783 76

Peritoneal macrophages (PMOs) are important components of the host defense against microbial infection in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Incubation of human PMOs with cell-free supernatant (BFS), prepared from Staphylococcus aureus, inhibited prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) production. Slot-blot analysis of cyclooxygenase-1 (Cox-1) and Cox-2 demonstrated a decrease in both Cox-1 (29%) and, to a greater extent, Cox-2 (65%) protein expression after BFS stimulation. When competitive polymerase chain reaction (PCR) was used, the peak levels of Cox-1 and Cox-2 messenger ribonucleic acid (mRNA) in unstimulated PMOs were 0.304+/-0.13 pmol/L and 9.61+/-2.84 pmol/L (mean+/-SEM, n = 3), respectively. After exposure of samples to BFS for 30 minutes, the level of Cox-2 mRNA was reduced to 0.59+/-0.449 pmol/L (16-fold reduction, p < 0.05), and the level of Cox-1 mRNA was reduced to 0.02+/-0.002 pmol/L (15-fold reduction, p < 0.05). In contrast, these same PMOs showed an increased expression of IL-6 mRNA and increased secretion of IL-6 protein. These results indicate that prostaglandin production in PMOs is regulated by alterations in both immunoreactive Cox-1 and Cox-2. The down-regulation of Cox metabolism in these cells is primarily related to the delayed and depressed increase in the Cox-2 gene product.
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PMID:Staphylococcal exoproducts down-regulate cyclooxygenase 1 and 2 in peritoneal macrophages. 901 88

Thromboxane (TX) A2 effects in the kidneys include contraction of glomerular mesangial cells and intrarenal vascular tissue. A kidney cDNA encoding a TX receptor expressed in rat renal glomeruli and rat renal arterial smooth muscle cells has been reported. However, TXA2 receptors in human kidneys have not been documented. The purpose of this study was to identify and characterize TXA2 receptors in glomeruli and intrarenal arteries isolated from human kidneys. Normal kidneys, not used for transplant because of technical reasons, were kept at -70 degrees C and used for research purposes. The glomeruli and intrarenal arteries were isolated from renal cortical tissue by a mechanical sieving technique. The equilibrium dissociation constant and receptor number were determined by nonlinear analysis of binding inhibition data. The data were generated in radioreceptor assays using [125I]-BOP, a stable analog of TXA2. The dissociation constants (mean +/- SEM) for binding of I-BOP to human glomeruli and intrarenal arterial membranes were 6.6 +/- 1.1 nM (n = 7) and 20 +/- 6 nM (n = 7), respectively (p < 0.05). The receptor number was 311 +/- 91 fmol/mg protein (n = 7) in glomeruli and 74 +/- 16 fmol/mg protein (n = 7) in intrarenal arterial membranes (p < 0.04). The order of specificity of TXA2 analogs for [125I]-BOP binding sites was similar in glomeruli and in arterial membranes and was I-BOP > or = U46619 > or = pinane TXA2 > or = carbocyclic TXA2 > or = PGH2. These findings provide direct evidence for the presence of specific, high-affinity [125I]-BOP binding sites in human renal glomeruli and extraglomerular vascular tissue. These data also indicate that the human binding sites have higher affinity for the TXA2 agonist I-BOP than for PGH2.
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PMID:Thromboxane receptors in human kidney tissues. 1040 13

Recent studies suggest that lipocalin-type prostaglandin (PG) D synthase (L-PGDS), which converts PGH2 to PGD2, is implicated in the pathogenesis of atherosclerosis. However, clinical evidence for the association between serum L-PGDS levels and atherosclerosis has not been reported. In this study, we measured the serum L-PGDS concentration using sandwich enzyme-linked immunosorbent assay (ELISA) and investigated the association with traditional cardiovascular risk factors and surrogate atherosclerotic indices, such as the maximum score of the intima-media complex thickness of the carotid artery (C-IMT(max)) and the brachial-ankle pulse wave velocity (ba-PWV), in 500 non-treated asymptomatic subjects. The serum concentration of L-PGDS was 0.56+/-0.01 (mean+/-SEM, range 0.25-1.27, median 0.54) mg/L. Serum L-PGDS levels increased with age and were higher in men than in women. Serum L-PGDS was higher in subjects with hypertension and increased with increasing numbers of the traditional atherosclerotic risk factors. When the subjects were divided into four groups according to the levels of serum L-PGDS, the age-adjusted values of C-IMT(max) and ba-PWV were significantly increased in subjects with higher serum L-PGDS levels (quartile 3 and quartile 4) compared to those in the lowest quartile (quartile 1), for both genders. Multiple regression analysis including risk factors revealed that serum L-PGDS was an independent determinant for ba-PWV (beta=0.130, p<0.001). Serum L-PGDS tended to associate with C-IMT(max) but was not statistically significant (beta=0.084, p=0.075). In conclusion, our results suggest that an increase in serum L-PGDS concentration is associated with the progression of atherosclerosis.
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PMID:Association of serum lipocalin-type prostaglandin D synthase levels with subclinical atherosclerosis in untreated asymptomatic subjects. 1901 1

The objective of this study was to determine whether the use of the most commonly prescribed antibiotics and non-steroidal anti-inflammatory drugs in childhood could disturb enamel mineralization. Forty-two Swiss mice were divided into seven groups: controls; amoxicillin; amoxicillin/clavulanate; erythromycin; acetaminophen; ibuprofen and celecoxib, to inhibit cyclooxygenase 2 (COX2). SEM-EDX analysis was conducted on all cusps of the third molars. Calcium (Ca), phosphorus (P), aluminum, potassium, sodium, magnesium and chlorine were quantified. The stoichiometric Ca/P molar ratios were calculated. Immunohistochemical quantification of COX2 in incisors was carried out by image analysis using COX2-specific immunostaining. Groups treated with antibiotics showed no significant differences in the content of the chemical elements. Only acetaminophen and celecoxib showed a significant decrease in Ca and P compared with the control samples. Ca/P ratios showed no difference. Groups treated with amoxicillin, amoxicillin/clavulanate, erythromycin and acetaminophen showed significantly lower amounts of immunoreactive COX2 at the enamel organ maturation stage of the mouse incisors. Our results suggest that COX2 is involved in the maturation stage of the enamel organ and that its inhibition would appear to alter amelogenesis, producing hypomineralization.
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PMID:Effect of antibiotics and NSAIDs on cyclooxygenase-2 in the enamel mineralization. 2951 75