Regulation of cyclooxygenase-2 and prostaglandin F synthase gene expression by steroid hormones and interferon-tau in bovine endometrial cells

Estradiol (E2) and progesterone are responsible for regulating PG synthesis in the endometrium during the estrous cycle and interferon-tau (IFN-tau) alters PG synthesis during early pregnancy in ruminants. In this study, we examined the effects of these steroid hormones and recombinant bovine IFN-tau (rbIFN-tau) on PG production and on cyclooxygenase-2 (COX-2) and PG F (PGF) synthase (PGFS) gene expression in isolated endometrial cells. E2 decreased both PGF2alpha and PG E2 (PGE2) whereas progesterone increased PGF2alpha secretion in epithelial cells. Steroid hormones had no effect on PG production in stromal cells. rbIFN-tau attenuated both PGF2alpha and PGE2 production in epithelial cells and enhanced their production, and the ratio of PGE2 to PGF2alpha, in stromal cells. Northern blot analysis showed that E2 and rbIFN-tau decreased COX-2 messenger RNA (mRNA) levels in epithelial cells. Conversely, rbIFN-tau increased COX-2 mRNA in stromal cells. Furthermore, rbIFN-tau decreased PGFS mRNA in both cell types and this was associated with the increase in PGE2/PGF2alpha ratio. These results show that the regulation of PG synthesis by steroid hormones is different in endometrial epithelial and stromal cells in vitro. The attenuation of PGF2alpha secretion from epithelial cells and increased PGE2 production in stromal cells by rbIFN-tau are modulated by steroid hormones.     

Piperazinyl oxazolidinone antibacterial agents containing a pyridine, diazene, or triazene heteroaromatic ring

Oxazolidinones are a novel class of synthetic antibacterial agents active against gram-positive organisms including methicillin-resistant Staphylococcus aureus as well as selected anaerobic organisms. Important representatives of this class include the morpholine derivative linezolid 2, which is currently in phase III clinical trials, and the piperazine derivative eperezolid 3. As part of an investigation of the structure-activity relationships of structurally related oxazolidinones, we have prepared and evaluated the antibacterial properties of a series of piperazinyl oxazolidinones in which the distal nitrogen of the piperazinyl ring is substituted with a six-membered heteroaromatic ring. Compounds having MIC values 相似文献   

Hematopoietic bone marrow hyperplasia: correlation of spinal MR findings, hematologic parameters, and bone mineral density in endurance athletes

To clarify the effects of obstructive jaundice on the liver, sequential changes of hepatic energy charge, the concentrations of adenine nucleotides and malondialdehyde, DNA synthesis rate, and histology of the liver were examined on the day before and Days 1, 2, 4, 7, and 14 after biliary obstruction in rats and compared with those of sham-operated controls. Foci of necrotic hepatocytes were present on Days 1 and 2 and mitoses of the hepatocytes were frequently observed with a peak on Day 2 in the jaundiced liver. Marked proliferation of bile ductules were subsequently observed on Days 7 and 14, resembling biliary cirrhosis. The DNA synthesis rate was significantly activated after bile duct obstruction with its peak on Day 2, more than nine times higher than the control value and returned to the control level on Day 14. Hepatic ATP concentration and energy charge gradually declined with prolonged jaundice and significantly lower levels persisted after Day 7 compared with the controls. The malondialdehyde level in the jaundiced liver gradually increased and became significantly higher on Day 14. We conclude that obstructive jaundice decreases hepatic energy charge and increases the lipoperoxide level. In the initial stage of obstructive jaundice, the hepatocytes proliferate associated with activated DNA synthesis probably to compensate hepatic damage; however, prolonged obstructive jaundice induces functional hepatic injury possibly necessitating biliary drainage.     

Work patterns and occupational hazard exposures of North Carolina adolescents in 4-H clubs

PURPOSE: We used white-light confocal microscopy to identify the causative organisms in two patients with contact lens related keratitis. METHODS: The corneal infiltrates were examined by confocal microscopy and corneal specimens were obtained for culture. RESULTS: In both patients, confocal microscopy revealed 1.5- to 2-micron diameter hyper-reflective bodies below the level of the epithelium. The sizes of these structures were consistent with those of bacteria. The corneal cultures from one patient grew Staphylococcus werneri and the cultures from the other patient grew Streptococcus viridans. CONCLUSIONS: The confocal microscope permitted the in vivo observation of what we believe to be bacteria in patients diagnosed with contact lens related keratitis.     

Accurate localization of mitral regurgitant defects using multiplane transesophageal echocardiography

BACKGROUND: Appropriate patient selection for surgical repair of the mitral valve depends on the specific location and mechanism of regurgitation, which, in turn, has necessitated a more detailed method to accurately describe mitral pathology. This study tests a strategy of using multiplane transesophageal echocardiography to systematically localize mitral regurgitant defects and compares these results with the surgical findings. METHODS: Fifty patients with mitral regurgitation underwent intraoperative transesophageal echocardiography for the evaluation of mitral pathology and potential repair. Mitral regurgitant defects were localized using a systematic strategy and a simple nomenclature that divides each mitral valve into six sections (three sections per leaflet) and each prosthetic sewing ring into six sections (60 radial degrees = one section). RESULTS: Thirty-nine patients with native mitral valves were studied, for a total of 234 sections evaluated. Eighty-seven of these sections contained regurgitant defects by transesophageal echocardiography (mean number of regurgitant defects per valve, 2.2; range, 1 through 6). There was agreement between the transesophageal echocardiographic and surgical localizations in 96% (224/234; p < 0.0001) of the sections. Eleven patients with prosthetic mitral valves were studied, for a total of 66 sections evaluated. Twenty-three of these sections contained paravalvular leaks by transesophageal echocardiography (mean number of leaks per prosthesis, 2.1; range, 1 through 6). There was agreement between the transesophageal echocardiographic and surgical localizations in 88% (58/66; p < 0.001) of the sections. CONCLUSIONS: This transesophageal echocardiographic strategy provides a systematic method to accurately localize mitral regurgitant lesions and has the potential to improve the preoperative assessment of patients with significant mitral regurgitation.     

Body habitus as a predictor of burn risk in children: do fat boys still get burned?

Previous research at this institute has demonstrated that heavy-for-age boys are more burn prone than their normal sized counterparts. As this study is now 26 years old, we reexamined the anthropomorphic indices of 372 children admitted to one burn center between January 1991 and July 1997 to determine if this trend was still evident. Male children were over-represented in the < or =5th and >95th percentiles for both height (p < 0.001, p < 0.05) and weight (p < 0.01, p < 0.001). Female children were over-represented in the < or =5th and > 95th percentiles for height (p < 0.01, p < 0.05). Twenty-eight percent of boys at or below the 5th percentile for weight were burned as a result of known or suspected intentional injury, compared to 5.9% of the entire pediatric burn population. (p < 0.0004). 'Fat boys' continue to be over-represented in the pediatric burn population. Additionally, in the more recent time period, boys at or below the 5th percentile for height or weight and girls= < 5th percentile or >95th percentile for height are also over-represented. The increased frequency of burn injury in small-for-age children may reflect an increased risk of burn injury secondary to neglect or nonaccidental trauma.     

Pharmacodynamic efficacy, clinical safety, and outcomes after prolonged platelet Glycoprotein IIb/IIIa receptor blockade with oral xemilofiban: results of a multicenter, placebo-controlled, randomized trial

BACKGROUND: Parenteral administration of platelet glycoprotein IIb/IIIa (GP IIb/IIIa) receptor blockers can reduce ischemic complications of coronary angioplasty. Orally active GP IIb/IIIa blockers may allow more sustained receptor antagonism with the potential for long-term secondary prevention. The pharmacodynamic efficacy, clinical safety, and outcomes after prolonged receptor blockade with an orally active GP IIb/IIIa antagonist are not known. The Oral Glycoprotein IIb/IIIa Receptor Blockade to Inhibit Thrombosis (ORBIT) Trial is a multicenter, placebo-controlled, randomized trial of xemilofiban, an oral platelet GP IIb/IIIa blocking agent, administered to patients after percutaneous coronary intervention. METHODS AND RESULTS: After successful elective percutaneous coronary intervention, 549 patients were randomized to receive either placebo or xemilofiban in a dose of 15 or 20 mg. Stented patients randomized to placebo also received ticlopidine 250 mg orally BID for 4 weeks. Patients who received abciximab during the coronary intervention and who were randomized to receive xemilofiban were administered a reduced dosage (10 mg TID for 2 weeks) followed by the randomized maintenance dose of 15 or 20 mg BID for 2 more weeks. All patients received 325 mg aspirin PO QD. Ex vivo platelet aggregation in response to 20 micromol/L ADP and 4 microg/mL collagen was measured over time after the initial dose of study drug and at days 14 and 28 of long-term therapy in 230 patients. All patients were followed clinically for 90 days. Xemilofiban inhibited platelet aggregation to both ADP and collagen with peak levels of inhibition that were similar at 14 and 28 days of long-term oral therapy. Plasma levels of xemilofiban correlated with the degree of platelet inhibition. Peak platelet inhibition on day 1 correlated with the subsequent occurrence of insignificant or mild bleeding events. Although this study was not powered to evaluate differences in clinical outcomes, a trend (P=0.04) was observed for reduction of cardiovascular events at 3 months in patients not treated with abciximab who received the highest dose (20 mg) of xemilofiban studied. CONCLUSIONS: Xemilofiban inhibited platelet aggregation and was well tolerated during 28 days of long-term oral therapy. The observed trend in reduction of cardiovascular events in follow-up awaits confirmation in the larger-scale phase III study (EXCITE trial) currently in progress.