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Biomedical subjects

E Wong

Publications and source records attributed to E Wong.

At least 55 records · Page 3Linked to original sources
PubMed2003

Cough frequency in children with stable asthma: correlation with lung function, exhaled nitric oxide, and sputum eosinophil count.

BACKGROUND: A study was undertaken to assess the correlation between cough frequency in asthmatic children with lung function and two non-invasive markers of airway inflammation. METHODS: Thirty two children of median age 12.0 years (interquartile range (IQR) 9.5-13.4) with stable asthma were recruited. They underwent spirometric testing, exhaled nitric oxide (eNO) measurement, sputum induction for differential cell count, and ambulatory cough monitoring over 17 hours and 40 minutes. Coughing episodes were counted both as individual spikes and as clusters. RESULTS: Complete cough frequency data were available in 29 children (90%) and their median forced expiratory volume in 1 second (FEV1) and eNO were 88.5% (IQR 79.5-98) and 23.9 ppb (IQR 11.4-41.5), respectively. The median number of cough episodes was 14 (IQR 7.0-24.0) which was significantly higher than that of normal children (6.7 (IQR 4.1-10.5), p<0.001). Sputum induction was successful in 61% of the subjects; the median induced sputum eosinophil count was 0.05% (IQR 0-9.0). Cough frequency was found to have a significant positive correlation with eNO (Spearman's r =0.781, p<0.001) but not with FEV1 or sputum eosinophil count (r =-0.270, p=0.157; r =0.173, p=0.508, respectively). CONCLUSIONS: Children with stable asthma have increased cough frequency compared with normal controls and cough frequency was greater during the day than at night. Cough may be a more sensitive marker of airway inflammation than simple spirometry.

Adolescent↗
PubMed2002

Pulmonary rehabilitation for chronic obstructive pulmonary disease.

BACKGROUND: The widespread application pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) should be preceded by demonstrable improvements in function attributable to the programs. This review updates that reported by Lacasse et al Lancet 1996; 748:1115-1119. OBJECTIVES: To determine the impact of rehabilitation on health-related quality of life (QoL) and exercise capacity in patients with COPD. SEARCH STRATEGY: The 14 randomized controlled trials (RCTs) included in the original meta-analysis were included. Additional RCTs were identified from the Cochrane Airways Group's registry of COPD RCTs using the strategy: [exp, lung diseases, obstructive] and [exp, rehabilitation or exp, exercise therapy] and [research design or longitudinal studies or evaluation study or randomized controlled trial]. Abstracts presented at American Thoracic Society 1980-2000, American College of Chest Physicians 1980-2000 and European Respiratory Society 1987-2000 were also searched. SELECTION CRITERIA: RCTs of rehabilitation in patients with COPD in which quality of life (QoL) and/or functional (FEC) or maximal (MEC) exercise capacity were measured. Rehabilitation was defined as exercise training for at least 4 weeks with or without education and/or psychological support. Control groups received conventional community care without rehabilitation. DATA COLLECTION AND ANALYSIS: Weighted mean differences (WMD) were calculated using a random-effects model. Missing data from the primary study reports were requested from the authors. MAIN RESULTS: 23 RCTs met the inclusion criteria. Statistically significant improvements were found for all the outcomes. In three important domains of QoL (Chronic Respiratory Questionnaire scores for Dyspnea, Fatigue and Mastery), the effect was larger than the minimal clinically important difference of 0.5 units using this instrument. For example Dyspnoea score: WMD 0.98 units, 95% Confidence Interval (95% CI) 0.74 - 1.22 units; n=9 trials. For FEC and MEC, the effect was small and a little below the threshold of clinical significance for the 6- minute walking distance: WMD 49 m, 95% CI: 26 - 72 m; n=10 trials. REVIEWER'S CONCLUSIONS: Rehabilitation relieves dyspnea and fatigue and enhances patients' sense of control over their condition. These improvements are moderately large and clinically significant. The average improvement in exercise capacity was modest. Rehabilitation forms an important component of the management of COPD.

Dyspnea↗
PubMed2002

Incidence and risk factors for microbial keratitis in Hong Kong: comparison with Europe and North America.

PURPOSE: To establish the incidence, etiology and risk factors for microbial keratitis (MK) in Hong Kong. METHODS: Two hundred and twenty-three new cases of presumed MK were recruited over a period of 17 months and comprehensive microbiologic studies performed. A nested case-control study was pursued for patients wearing contact lenses (CLW) to determine risk factors for MK with regards to types of CLW and hygiene practice. RESULTS: Of the 223 patients recruited, 59 (26%) wore contact lenses. Corneal scrapes yielded positive cultures from 77 patients (35% overall, 56 non-CLW, 21 CLW). Two hundred and six CLW volunteers were recruited to participate in the case-control study, of whom 135 were matched with 45 CLW patients. The annual incidence of MK was 0.63 per 10,000 population and 3.4 per 10,000 CLW with rates for daily, extended and rigid lens wear of 3.09, 9.30 and 0.44 per 10,000 CLW respectively. Pseudomonas aeruginosa was the dominant bacterial pathogen. Six cases of Acanthamoeba keratitis occurred, five in CLW (incidence 0.33 per 10,000 CLW) and one following corneal abrasion. Non-CLW developed MK at a peak age of 73, which is 10 years younger than expected for Scotland and USA. CONCLUSIONS: Previous ocular surface disease and trauma were the main risk factors for MK in Hong Kong. CLW appears at least as safe as that found in Scotland and the USA. Acanthamoeba keratitis was detected but with an incidence rate five times lower than Scotland. Factors predisposing hydrogel CLWs to MK, that were statistically significant, included overnight wear, poor hygiene and smoking.

Acanthamoeba Keratitis↗
PubMed2002

Changes in serum leptin concentration after corticosteroid treatment in preterm infants.

UNLABELLED: The aim of this study was to investigate the effect of postnatal systemic dexamethasone on serum leptin, insulin and hormones of the hypothalamic-pituitary-adrenal (HPA) axis in preterm, very low birthweight (VLBW) infants. Nineteen VLBW infants who received a 3 wk dose tapering course of dexamethasone for treatment of bronchopulmonary dysplasia were prospectively enrolled. Blood for hormone assays was collected immediately before the start of the dexamethasone course (T(d-per)), 3 wk after commencement of the drug (T(d-end)) and 2 wk after dexamethasone treatment had been stopped (T(d-post)). In addition, 28 VLBW infants who participated in a concurrent longitudinal leptin study within the same period but did not receive corticosteroid had their serum leptin and insulin concentrations serially monitored. Blood specimens for the latter group of infants were obtained at 2 (T(wk-2)), 5 (T(wk-5)) and 7 (T(wk-7)) wk of postnatal age. Serum leptin and insulin at T(d-end) were significantly increased, whereas plasma ACTH and serum cortisol were significantly suppressed compared with the pretreatment (T(d-pre)) levels in the corticosteroid group (p < 0.0001 for leptin and insulin; p < 0.05 and p < 0.001 for ACTH and cortisol, respectively). In contrast, serum leptin and insulin at weeks 5 (T(wk-5)) and 7 (T(wk-7)) did not differ significantly from their respective levels at week 2 (T(wk-2)) in the non-treatment group. CONCLUSION: The administration of systemic corticosteroid resulted in significant increases in serum leptin and insulin, but marked suppression of hormones of the HPA axis. The effect of dexamethasone on the "adipoinsular" and HPA axes was transient and reversible. The adipoinsular axis in preterm infants is likely to be functional and active at an early stage of human development, and leptin may regulate energy balance in VLBW infants in the early postnatal period. Corticosteroids may, through the adipoinsular axis or its associated pathways, mediate in the regulation of body weight in preterm neonates.

Adrenocorticotropic Hormone↗
PubMed2002

Use of tonsil size in the evaluation of obstructive sleep apnoea.

AIMS: (1) To determine the extent to which tonsil size contributes to the severity of obstructive sleep apnoea (OSA) in children; and (2) to assess the use of tonsillar-pharyngeal (TP) ratio in differentiating patients with different severity of OSA. METHODS: Lateral neck radiograph was performed on 35 children referred consecutively to a university paediatric chest clinic for suspected OSA secondary to tonsillar hypertrophy. The tonsil size was determined by measuring the TP ratio on the radiographs. The severity of OSA was assessed by overnight polysomnography. RESULTS: A total of 24 boys and 11 girls (median age 6.2 years) were studied. All presented with symptoms of OSA, and tonsillar hypertrophy was detected on clinical examination. The median apnoea-hypopnoea index (AHI) was 16.93 (interquartile range: 8.41 to 28.29). The median TP ratio was 0.76 (interquartile range: 0.65 to 0.80). AHI was positively correlated with the TP ratio. The clinical tonsil size did not correlate with the AHI or the TP ratio. Using a TP ratio of 0.479, the sensitivity and specificity in predicting cases with moderate/severe OSA (AHI >10) were 95.8% and 81.8% respectively, while the positive and negative predictive values were 92.0% and 90.0% respectively. CONCLUSIONS: Results show that in a population of children with OSA, tonsillar hypertrophy as assessed by lateral neck radiograph correlates positively with the severity of obstructive sleep apnoea. The TP ratio has high sensitivity and specificity in predicting those with moderate/severe disease and this feature may be used as a clinical screening method in prioritising patients with OSA for further assessment.

Child↗
PubMed2002

Respiratory function in patients with thalassaemia major: relation with iron overload.

AIMS: (1) To determine the pattern of respiratory impairment in children with thalassaemia major (TM); (2) to assess the relation between the degree of respiratory impairment and total body iron content. METHODS: Twenty nine TM patients were recruited. All underwent physical examination, standardised pulmonary function tests (spirometry, lung volume, and single breath diffusion capacity for carbon monoxide), and magnetic resonance imaging measurements of the liver. Serum ferritin was measured. The signal intensity ratio of liver to that of paraspinal muscle (T1 weighted sequence) and serum ferritin were used as surrogate index of body iron content. RESULTS: Sixteen boys and 13 girls (median age 14.2 years) were studied. None had clinical evidence of congestive heart failure. Sixteen had normal lung function. Impairment of diffusion capacity (median DL(co) 83.5% predicted) was the most common abnormality, being observed in 34% of patients. Pure restrictive and obstructive ventilatory impairment was found in one and two patients respectively. Five patients had a combination of ventilation and diffusion defects. There was no correlation between the degree of impairment of each respiratory abnormality and body iron content. CONCLUSION: Diffusion impairment was the commonest abnormality found in our cohort of paediatric TM patients. Our data did not support the notion that respiratory function impairment was correlated with body iron content.

Adolescent↗
PubMed2002

Changes in markers of bone metabolism during dexamethasone treatment for chronic lung disease in preterm infants.

AIM: To characterise the change in serum and urinary bone markers in the early postnatal period, and to assess the effect of systemic corticosteroid on bone metabolism in preterm infants. METHODS: Bone formation was quantified by measurement of serum concentrations of bone specific alkaline phosphatase (BALP) and osteocalcin. Bone resorption was measured by monitoring creatinine adjusted urinary deoxypyridinoline (Dpd) concentration. Blood and urinary samples were collected from corticosteroid treated infants (n = 19) immediately before the start (T(d-pre)), three weeks after the start (T(d-end)), and two (T(d-post2)) and four weeks (T(d-post4)) after the end of the dexamethasone course. Untreated patients (n = 30) had specimens taken at week 3 (T(wk-3)), 6 (T(wk-6)), 8 (T(wk-8)), and 10 (T(wk-10)) of postnatal age. RESULTS: Serum concentrations of BALP and osteocalcin at T(d-end) were significantly lower than pretreatment levels and the levels at the corresponding time point (T(wk-6)) of the non-treatment group. In contrast, urinary Dpd concentration at T(d-end) was not significantly decreased compared with the pretreatment level. However, it was significantly lower than the urinary Dpd concentration at T(wk-6) of the non-treatment group. The rate of increase in lower leg length was significantly higher in the non-treatment group between weeks 3 and 6 than in the corresponding period during dexamethasone treatment in the corticosteroid group. CONCLUSION: Systemic corticosteroid causes appreciable suppression of serum BALP and osteocalcin and, to a lesser extent, urinary Dpd. The results suggest that corticosteroid inhibits bone growth mainly by decreasing bone formation.

Alkaline Phosphatase↗
PubMed2002

Heterosexual outbreak of infectious syphilis: epidemiological and ethnographic analysis and implications for control.

This study describes the epidemiology and ethnography of an outbreak of infectious syphilis in Vancouver, British Columbia. Between 1996 and 1999, British Columbias's rate of infectious syphilis rose from 0.5 to 3.4 per 100,000, with a dense concentration of cases among sex trade workers, their clients, and street-involved people in the downtown eastside area of Vancouver. Sexual networks were imported cases with secondary spread (dyads and triads), large densely connected dendritic networks of sex trade workers and clients, or occasional starburst networks among gay men. Only 232 of 429 partners were documented as having been treated (54% of those named, or 0.9 per case). The geographical and demographic concentration of this outbreak led to consideration of a programme of focused mass treatment with single dose azithromycin.

Adolescent↗
PubMed2002

Reference ranges and factors affecting the human corticotropin-releasing hormone test in preterm, very low birth weight infants.

This prospective study aims to investigate the factors that influence the human CRH (hCRH) test and to provide reference ranges for plasma corticotropin (ACTH) and serum cortisol concentrations of the stimulation test in preterm, very low birth weight (VLBW) infants. Two hundred twenty-six hCRH tests were performed on 137 VLBW infants at d 7 and 14 of life. Plasma ACTH did not differ significantly between infants whose mothers did not receive antenatal corticosteroids (group 1) and those whose mothers received one or two doses (group 2) or more than two doses (group 3) of the drug. However, plasma ACTH levels at d 7 were found to be significantly higher in infants with severe lung disease who required intermittent positive-pressure ventilation (IPPV) or high-frequency oscillation ventilation (HFOV), compared with those who had milder pulmonary disease and did not require mechanical ventilation or needed only continuous positive airway pressure (CPAP) support (P < 0.011). A significantly higher rate of increase in plasma ACTH concentration at d 7 was also observed in infants whose mothers suffered from antepartum hemorrhage (P < 0.016). In contrast, infants in group 2 had significantly lower serum cortisol, compared with group 1 infants (P < 0.05), whereas group 3 infants did not have serum cortisol levels significantly different from those of patients in group 1 or 2. Significant positive correlation between serum cortisol at d 7 and the time interval between the last dose of antenatal dexamethasone and delivery was also observed in group 3 infants (r > 0.33, P < 0.045). In addition, infants who required IPPV or HFOV had significantly lower serum cortisol at d 7 (P < 0.0001), but this pattern of cortisol response was reversed on d 14, with infants requiring IPPV or HFOV having significantly higher serum cortisol (P < 0.036). The reference ranges for plasma ACTH and serum cortisol concentrations of the hCRH test at d 7 and 14 were also provided for group 1 and group 2 infants. This study demonstrates that even one or two doses of antenatal corticosteroids cause adrenal suppression in VLBW infants. Maternal antepartum hemorrhage also influences the pituitary response of preterm newborns in the first week of life. The change in the pattern of cortisol response in sick ventilated (IPPV or HFOV) infants during the first 2 wk of life suggests that a proportion of preterm infants may have inadequate adrenal response to stress in early postnatal life, but it is likely that rapid adaptation of the hypothalamic-pituitary-adrenal axis results in enhanced and more appropriate cortisol response by d 14. The percentile distribution of plasma ACTH and serum cortisol responses provides useful statistical reference data for interpretation of the hCRH test in VLBW infants and may also assist in facilitating the use of corticosteroids replacement therapy in cases with clinical manifestations suggestive of adrenal insufficiency.

Adrenal Cortex Hormones↗
PubMed2001

The distinct spectra of tumor-associated Apc mutations in mismatch repair-deficient Apc1638N mice define the roles of MSH3 and MSH6 in DNA repair and intestinal tumorigenesis.

In mammalian cells, mismatch recognition has been attributed to two partially redundant heterodimeric protein complexes of MutS homologues, MSH2-MSH3 and MSH2-MSH6. We have conducted a comparative analysis of Msh3 and Msh6 deficiency in mouse intestinal tumorigenesis by generating Apc1638N mice deficient in Msh3, Msh6 or both. We have found that Apc1638N mice defective in Msh6 show reduced survival and a 6-7-fold increase in intestinal tumor multiplicity. In contrast, Msh3-deficient Apc1638N mice showed no difference in survival and intestinal tumor multiplicity as compared with Apc1638N mice. However, when Msh3 deficiency is combined with Msh6 deficiency (Msh3(-/-)Msh6(-/-)Apc1638N), the survival rate of the mice was further reduced compared to Msh6(-/-)Apc(1638N) mice because of a high multiplicity of intestinal tumors at a younger age. Almost 90% of the intestinal tumors from both Msh6(-/-)Apc1638N and Msh3(-/-)Msh6(-/-)Apc1638N mice contained truncation mutations in the wild-type Apc allele. Apc mutations in Msh6(-/-)Apc1638N mice consisted predominantly of base substitutions (93%) creating stop codons, consistent with a major role for Msh6 in the repair of base-base mismatches. However, in Msh3(-/-)Msh6(-/-)Apc1638N tumors, we observed a mixture of base substitutions (46%) and frameshifts (54%), indicating that in Msh6(-/-)Apc1638N mice frameshift mutations in the Apc gene were suppressed by Msh3. Interestingly, all except one of the Apc mutations detected in mismatch repair-deficient intestinal tumors were located upstream of the third 20-amino acid beta-catenin binding repeat and before all of the Ser-Ala-Met-Pro repeats, suggesting that there is selection for loss of multiple domains involved in beta-catenin regulation. Our analysis therefore has revealed distinct mutational spectra and clarified the roles of Msh3 and Msh6 in DNA repair and intestinal tumorigenesis.

Animals↗
PubMed2001

Multiple cadherin extracellular repeats mediate homophilic binding and adhesion.

The extracellular homophilic-binding domain of the cadherins consists of 5 cadherin repeats (EC1-EC5). Studies on cadherin specificity have implicated the NH(2)-terminal EC1 domain in the homophilic binding interaction, but the roles of the other extracellular cadherin (EC) domains have not been evaluated. We have undertaken a systematic analysis of the binding properties of the entire cadherin extracellular domain and the contributions of the other EC domains to homophilic binding. Lateral (cis) dimerization of the extracellular domain is thought to be required for adhesive function. Sedimentation analysis of the soluble extracellular segment of C-cadherin revealed that it exists in a monomer-dimer equilibrium with an affinity constant of approximately 64 microm. No higher order oligomers were detected, indicating that homophilic binding between cis-dimers is of significantly lower affinity. The homophilic binding properties of a series of deletion constructs, lacking successive or individual EC domains fused at the COOH terminus to an Fc domain, were analyzed using a bead aggregation assay and a cell attachment-based adhesion assay. A protein with only the first two NH(2)-terminal EC domains (CEC1-2Fc) exhibited very low activity compared with the entire extracellular domain (CEC1-5Fc), demonstrating that EC1 alone is not sufficient for effective homophilic binding. CEC1-3Fc exhibited high activity, but not as much as CEC1-4Fc or CEC1-5Fc. EC3 is not required for homophilic binding, however, since CEC1-2-4Fc and CEC1-2-4-5Fc exhibited high activity in both assays. These and experiments using additional EC combinations show that many, if not all, the EC domains contribute to the formation of the cadherin homophilic bond, and specific one-to-one interaction between particular EC domains may not be required. These conclusions are consistent with a previous study on direct molecular force measurements between cadherin ectodomains demonstrating multiple adhesive interactions (Sivasankar, S., W. Brieher, N. Lavrik, B. Gumbiner, and D. Leckband. 1999. PROC: Natl. Acad. Sci. USA. 96:11820-11824; Sivasankar, S., B. Gumbiner, and D. Leckband. 2001. Biophys J. 80:1758-68). We propose new models for how the cadherin extracellular repeats may contribute to adhesive specificity and function.

Animals↗
PubMed2001

E-cadherin suppresses cellular transformation by inhibiting beta-catenin signaling in an adhesion-independent manner.

E-cadherin is a tumor suppressor protein with a well-established role in cell-cell adhesion. Adhesion could contribute to tumor suppression either by physically joining cells or by facilitating other juxtacrine signaling events. Alternatively, E-cadherin tumor suppressor activity could result from binding and antagonizing the nuclear signaling function of beta-catenin, a known proto-oncogene. To distinguish between an adhesion- versus a beta-catenin signaling-dependent mechanism, chimeric cadherin constructs were expressed in the SW480 colorectal tumor cell line. Expression of wild-type E-cadherin significantly inhibits the growth of this cell line. Growth inhibitory activity is retained by all constructs that have the beta-catenin binding region of the cytoplasmic domain but not by E-cadherin constructs that exhibit adhesive activity, but lack the beta-catenin binding region. This growth suppression correlates with a reduction in beta-catenin/T cell factor (TCF) reporter gene activity. Importantly, direct inhibition of beta-catenin/TCF signaling inhibits the growth of SW480 cells, and the growth inhibitory activity of E-cadherin is rescued by constitutively activated forms of TCF. Thus, the growth suppressor activity of E-cadherin is adhesion independent and results from an inhibition of the beta-catenin/TCF signaling pathway, suggesting that loss of E-cadherin expression can contribute to upregulation of this pathway in human cancers. E-cadherin-mediated growth suppression was not accompanied by overall depletion of beta-catenin from the cytosol and nucleus. This appears to be due to the existence of a large pool of cytosolic beta-catenin in SW480 cells that is refractory to both cadherin binding and TCF binding. Thus, a small pool of beta-catenin that can bind TCF (i.e., the transcriptionally active pool) can be selectively depleted by E-cadherin expression. The existence of functionally distinct pools of cytosolic beta-catenin suggests that there are mechanisms to regulate beta-catenin signaling in addition to controlling its level of accumulation.

Binding Sites↗
PubMed2001

The invariant F283 and its strategic position in the hydrophobic cleft of Streptomyces jumonjinensis isopenicillin N synthase active site are functionally important.

Isopenicillin N synthase (IPNS) and related non-haem iron-binding enzymes including deacetoxycephalosporin C synthase (DAOCS) are proposed to have structurally similar active centers. Sequence alignment and computational structural analyses of predicted structures revealed 11 highly conserved hydrophobic amino acid residues in 134 IPNS-related enzymes form a contiguous hydrophobic patch in the IPNS active center, wherein F283 is strategically positioned. The investigation of single and double mutations at F283, adjacent (L284) and proximal sites (N285 and S216) of Streptomyces jumonjinensis IPNS advocate the explicit importance of the phenyl ring at position 283. A similarly placed phenylalanine (F264) in DAOCS was found to be also crucial for its enzyme activity.

Amino Acid Sequence↗
PubMed2001

A method for fast 3D tracking using tuned fiducial markers and a limited projection reconstruction FISP (LPR-FISP) sequence.

This work demonstrates the feasibility of using wireless, tuned fiducial markers with a limited projection reconstruction-fast imaging with steady-state free precession sequence (LPR-FISP) to accurately obtain tracking information necessary for interactive scan plane selection in magnetic resonance imaging (MRI). The position and orientation of a rigid interventional device can be uniquely determined from the 3D coordinates of three fiducial markers mounted in a known configuration on the device. Three fiducial markers were tuned to the proton resonant frequency in a 0.2T open MR scanner and mounted to the surface of a cylindrical water phantom. An LPR-FISP sequence was developed to suppress the water phantom signal while preserving that of the fiducial markers through a nonselective low-tip-angle excitation and a dephaser gradient applied prior to data acquisition. A localization algorithm was developed to accurately calculate the 3D coordinates of the fiducial markers using four LPR-FISP projections in two orthogonal scan planes. The sequence repetition time (TR = 21 msec) and the limited projection set resulted in fast LPR-FISP coordinate acquisition times of approximately 170 msec with an accuracy (max error) of 3 mm on a 0.2T MR system. This fast, accurate tracking method provides the fundamental technology for interactive MRI scan plane definition for rigid interventional devices without the need for stereotactic cameras or reference frames.

Algorithms↗
PubMed2001

Effects of COX-2 inhibitors on aortic prostacyclin production in cholesterol-fed rabbits.

Prostacyclin (PGI(2)) is a potent vasodilator and inhibitor of platelet aggregation that is produced by prostacyclin synthase via the cyclooxygenase (COX) pathway of arachidonic acid metabolism. We investigated the potential role of COX-2 in the production of vasoactive prostanoids by aortic tissue in a rabbit model of dietary cholesterol-induced atherosclerosis. COX-1 was detected as the major isoform by immunoblot analysis in extracts from aortas of normal and 8 week cholesterol-fed animals with COX-2 being induced in atherosclerotic plaques from cholesterol-fed animals. Aortic tissue from cholesterol-fed animals showed decreased levels of basal 6-keto-PGF(1 alpha) and PGE(2) production as compared to the normal controls but showed no difference with respect to their ability to synthesize these prostanoids in response to exogenous arachidonic acid. The highly selective COX-2 inhibitors rofecoxib and the furanone DFP at concentrations of up to 10 micromol/l had no effect on the arachidonic acid-dependent production of 6-keto-PGF(1 alpha), in contrast to indomethacin, which caused a complete inhibition at 0.5 micromol/l. Celecoxib caused a significant inhibition of 6-keto-PGF(1 alpha) at 10 micromol/l but had little effect when the dose was lowered to 1 micromol/l. Similar effects of these inhibitors were observed with respect to the production of PGE(2) and no major difference was observed between aortic tissues from normal and cholesterol-fed animals with regard to inhibitor sensitivity. These results indicate that in a rabbit model of early stage cardiovascular disease, the basal production of 6-keto-PGF(1 alpha) and PGE(2) by aortic tissue is decreased. Furthermore, COX-2 expression is induced in atherosclerotic plaques and may play a role in altering localized synthesis of prostanoids in these lesions but does not appear to significantly impact the arachidonic acid-dependent prostacylin production of aortic tissues, which is largely mediated by COX-1.

Animals↗