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Biomedical subjects

E Wong

Publications and source records attributed to E Wong.

At least 127 records · Page 7Linked to original sources
PubMed1998

The regional Monte Carlo method: a dose calculation method based on accuracy requirement.

In this work we propose the regional Monte Carlo (RMC) method of dose calculation. This method combines the Monte Carlo (MC) algorithm and a non-MC algorithm (such as the convolution method) for optimal speed and accuracy in dose calculation for both photon and electron beams and for various irradiation and patient geometries. For specific regions in the geometry where high accuracy is required but difficult to obtain with analytical or empirical calculations, such as critical organs surrounded by complicated inhomogeneities, the MC algorithm is used. For regions with simple geometries, or where a high degree of dose accuracy is not critical, the non-MC algorithm is used to increase speed. There are two aspects of the RMC method. The first one involves determining critical regions and boundaries, and the other involves the actual implementation and mixing of the two computational algorithms. Two examples of different geometries are used to illustrate the different ways to apply the RMC method. The possibility to extend the method to more complicated geometries and inhomogeneities, as well as the ability of the method to incorporate different calculation algorithms, are also discussed.

Algorithms↗
PubMed1998

Pain in Chinese cancer patients under palliative care.

Over a 4-month period, 218 Chinese patients with advanced cancer were admitted to a palliative care unit in Hong Kong. Ninety-five (44%) of them had pain. Of these 95, 70 (mean age 61.7 years) were evaluated with the visual analogue scale (VAS) and the numerical rating scale (NRS). Forty-two per cent of the 70 patients were illiterate. Eighty-three per cent had metastases. Eighty-seven per cent had pain due to the disease process. Forty-nine per cent had more than one pain, 54% had moderate pain and 20% had severe pain. The most common primary tumour was lung cancer. NRS scores strongly correlated with corresponding VAS scores, suggesting that NRS can routinely be used for pain intensity assessment in the Chinese. The study also showed that 64% of these patients with pain had moderate to severe disabilities to the basic activity of daily living, although there was no correlation between the severity of pain and the severity of disability.

Adult↗
PubMed1998

Development of a health-related quality-of-life questionnaire (PCOSQ) for women with polycystic ovary syndrome (PCOS).

OBJECTIVE: To develop a self-administered questionnaire for measuring health-related quality of life (HRQL) in women with polycystic ovary syndrome (PCOS). METHODS: We identified a pool of 182 items potentially relevant to women with PCOS through semistructured interviews with PCOS patients, a survey of health professionals who worked closely with PCOS women, and a literature review. One hundred women with PCOS completed a questionnaire in which they told us whether the 182 items were relevant to them and, if so, how important the issue was in their daily lives. We included items endorsed by at least 50% of women in the analysis plus additional items considered crucial by clinicians and an important subgroup of patients in a factor analysis. We chose items for the final questionnaire taking into account both item impact (the frequency and importance of the items) and the results of the factor analysis. RESULTS: Over 50% of the women with PCOS labelled 47 items as important to them. Clinicians chose 5 additional items from the infertility domain, 4 of which were identified as important by women who were younger, less educated, married, and African-American. The Cattell's Scree plot from a factor analysis of these 51 items suggested 5 factors that made intuitive sense: emotions, body hair, weight, infertility, and menstrual problems. We chose the highest impact items from these 5 domains to construct a final questionnaire, the Polycystic Ovary Syndrome Questionnaire (PCOSQ), which includes a total of 26 items and takes 10-15 minutes to complete. CONCLUSIONS: We have used established principles to construct a questionnaire that promises to be useful in measuring health-related quality of life. The questionnaire should be tested prior to, or concurrent with, its use in randomized trials of new treatment approaches.

Adult↗
PubMed1998

Errors in flow and pressure related to the arterial filter purge line.

The purge line is a necessary component on arterial filters, although its presence may affect the amount of flow reaching the patient as well as the pump outlet pressure in the extracorporeal circuit. In-vitro and clinical studies conducted to investigate these effects with a commonly used purge line showed that at flows less than 1.5 L/min, rates for pediatric or infant patients, the purge line diverts as much as 40% of the intended pump flow away from the patient. A small diameter resistance tube connected in series with the purge line reduced purge flow such that over 80% of the pump flow reached the patient. Pressure monitored at the arterial filter port with the purge line open could be as much as 45 mmHg lower than the pressure measured with the purge line closed to the filter. Studies should be done to determine if the arterial filter purge line compromises flow to the patient, and if an additional resistance to the purge line is appropriate to reduce the flow through it.

Arteries↗
PubMed1998

In vitro suppression of transforming growth factor-beta induced stimulation of glycosaminoglycan synthesis by acetylsalicylic acid and its reversal by misoprostol.

OBJECTIVE: To determine if acetylsalicylic acid (ASA) suppresses the stimulatory effects of transforming growth factor-beta (TGF-beta) and insulin-like growth factor-1 (IGF-1) on glycosaminoglycan (GAG) synthesis by cultured bovine articular chondrocytes (BAC), and whether such a suppression can be counteracted by the addition of misoprostol, a prostaglandin (PG) E1 analog. METHODS: Confluent cultures of BAC were pre-incubated for 2 days with ASA (Aspirin) (250 microg/ml), TGF-beta (10 ng/ml), IGF-1 (150 ng/ml), and misoprostol (80 ng/ml), separately and in different combinations, and for 2 more days with fresh medium and the same test agents in the presence of 35S-sulfate (10 microCi/ml). The radiolabelled GAG in the medium were then isolated, separated by cellulose acetate electrophoresis, and assayed for incorporated radioactivity, as a measure of GAG synthesis. RESULTS: TGF-beta, IGF-1, at their optimal concentrations, and misoprostol (80 ng/ml) stimulated GAG synthesis 2.6, 1.8, and 2.4-fold, respectively, of the control value, but ASA (250 microg/ml) showed no significant effect. ASA in combination with TGF-beta or misoprostol markedly suppressed the stimulation of GAG synthesis observed with either TGF-beta or misoprostol alone, but had no effect on the stimulation of GAG synthesis by IGF-1. Addition of misoprostol together with TGF-beta potentiated the stimulation of GAG synthesis by TGF-beta and abolished the suppressive effect of ASA on the stimulation of GAG synthesis by TGF-beta. Also, the magnitude of the stimulatory effect of misoprostol varied from batch to batch of misoprostol as well as for the same batch when it was added to the cultures either directly or after diluting with serum-free medium. CONCLUSION: In BAC cultures, ASA suppresses and misoprostol potentiates the stimulation of GAG synthesis by TGF-beta. Misoprostol also counteracts ASA induced suppression of the stimulation of GAG synthesis by TGF-beta.

Animals↗
PubMed1997

Hemispheric asymmetries in global and local processing: evidence from fMRI.

Functional magnetic resonance imaging (fMRI) was used to explore the brain substrate associated with global and local processing of visuospatial patterns. Systematic differences in activation, consistent with differences observed in reaction time data collected under conditions of visual hemifield presentation, were found in occipitotemporal regions of the right and left hemispheres. Within the right hemisphere, area of activation and fractional signal changes were greater under conditions of global processing than under local processing conditions. In the left hemisphere, activation to global and local input was high and comparable.

Adult↗
PubMed1997

Conversion of prostaglandin G/H synthase-1 into an enzyme sensitive to PGHS-2-selective inhibitors by a double His513 --> Arg and Ile523 --> val mutation.

Modeling of the active site of prostaglandin G/H synthase-2 (PGHS-2) onto PGHS-1 utilizing the known crystal structure of PGHS-1 shows that the only residues impinging directly on the active site that were not conserved in the two enzymes are His513 and Ile523 of PGHS-1 (Arg499 and Val509 of PGHS-2). These residues of human PGHS-1 were each mutated to the corresponding PGHS-2 residues (His513 --> Arg and Ile523 --> Val) and a double mutant (His513 --> Arg,Ile523 --> Val) containing both residues was also constructed. The mutant enzyme forms were expressed in COS-7 cells, and their properties were compared with those of the normal isoforms using microsomal membranes. The mutated enzyme forms all had apparent Km values within 1.4-fold that of the wild type enzyme, and the specific activity of the mutants were within 2-fold of that of PGHS-1. DuP697, NS-398, DFU, and SC-58125 are selective PGHS-2 inhibitors that act as time-dependent inhibitors of PGHS-2 and rapidly reversible competitive inhibitors of PGHS-1. The single Ile523 --> Val mutation increased the sensitivity to each of these selective inhibitors with most of the effect detected using instantaneous inhibition assays, except for DuP697, whose potency was further increased by preincubation with the enzyme. The double PGHS-1 His513 --> Arg, Ile523 --> Val mutant became more sensitive to inhibition by NS-398 and DFU than the single IV mutant, and time-dependent inhibition was observed. In contrast, the single HR mutation did not increase the sensitivity to inhibition by the selective PGHS-2 inhibitors. The potency of a selective PGHS-1 inhibitor, L-745,296, was decreased 5- and 13-fold in the HR and HR-IV mutants, respectively. All the results indicate that mutations of His513 and Ile523 residues of PGHS-1 can strongly increase sensitivity to selective PGHS-2 inhibition and restore time-dependent inhibition. They also suggest that the corresponding Arg499 and Val509 residues of PGHS-2 are essential determinants in differentiating between the interaction of nonselective NSAIDs and selective PGHS-2 inhibitors and their mechanism of action.

Amino Acid Sequence↗
PubMed1997

Cyclic AMP regulation of mouse proline-rich protein gene expression: isoproterenol induction of AP-1 transcription factors in parotid glands.

Proline-rich protein mRNAs are increased dramatically in the salivary glands of rats, mice, and hamsters upon treatment with the beta-agonist isoproterenol. Sequence comparisons between mice and hamster proline-rich protein genes identified conserved regions upstream from the transcription start site. Reporter plasmids containing these 5'-flanking sequences from a mouse proline-rich protein gene, MP2, were constructed and tested for transcriptional regulation by cAMP. Transient transfection experiments in mouse L-M cells showed that the upstream region -702 to -322 bp relative to the transcription start site is sufficient to confer cAMP induction on a heterologous promoter. Multiple copies of the AP-1 sequence elements within this region (-625 to -551) mediate the cAMP transcriptional response of reporter gene expression in L-M cells. L-M cell nuclear proteins and purified human c-jun protein bind to these upstream elements as determined by DNase I footprint analysis. Nuclear proteins isolated from mouse parotid glands protected the consensus AP-1 binding site 5'-TGAGTCA-3' (-592 to -586). The nuclear proteins interacting at this site were increased about sixfold in glands isolated from isoproterenol-treated mice when compared with glands from untreated mice. These results suggest that induction of AP-1 transcription factors in the parotid gland control the upregulation of some mouse salivary proline-rich proteins.

Adrenergic beta-Agonists↗
PubMed1997

Adenomatous polyposis coli tumor suppressor protein has signaling activity in Xenopus laevis embryos resulting in the induction of an ectopic dorsoanterior axis.

Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene are linked to both familial and sporadic human colon cancer. So far, a clear biological function for the APC gene product has not been determined. We assayed the activity of APC in the early Xenopus embryo, which has been established as a good model for the analysis of the signaling activity of the APC-associated protein beta-catenin. When expressed in the future ventral side of a four-cell embryo, full-length APC induced a secondary dorsoanterior axis and the induction of the homeobox gene Siamois. This is similar to the phenotype previously observed for ectopic beta-catenin expression. In fact, axis induction by APC required the availability of cytosolic beta-catenin. These results indicate that APC has signaling activity in the early Xenopus embryo. Signaling activity resides in the central domain of the protein, a part of the molecule that is missing in most of the truncating APC mutations in colon cancer. Signaling by APC in Xenopus embryos is not accompanied by detectable changes in expression levels of beta-catenin, indicating that it has direct positive signaling activity in addition to its role in beta-catenin turnover. From these results we propose a model in which APC acts as part of the Wnt/beta-catenin signaling pathway, either upstream of, or in conjunction with, beta-catenin.

Adenomatous Polyposis Coli Protein↗
PubMed1997

Characterization of autocrine inducible prostaglandin H synthase-2 (PGHS-2) in human osteosarcoma cells.

The human osteosarcoma 143.98.2 cell line was found to express high levels of prostaglandin synthase-2 (PGHS-2) without detectable levels of prostaglandin synthase-1 (PGHS-1) as measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblot analysis. Maximal levels of PGHS-2 induction were attained when the cells were grown beyond confluence. The osteosarcoma cells also secrete IL-1 alpha, IL-1 beta and TNF alpha in the culture medium. PGHS-2 expression was inducible by the exogenous addition of these cytokines as well as conditioned media from auto-induced cultures and inhibitable by treatment with dexamethasone. In contrast, undifferentiated U937 cells selectively express PGHS-1 as analyzed by RT-PCR and Western blotting. The effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the cellular PGE2 production mediated by each isoform of human PGHS were determined using osteosarcoma and undifferentiated U937 cells. When cells were preincubated with inhibitors to allow time-dependent inhibition prior to arachidonic acid stimulation, NS-398, CGP 28238, L-745,337, SC-58125 all behaved as potent (IC50 = 1-30 nM) and selective inhibitors of PGHS-2, in contrast to indomethacin, flurbiprofen or diclofenac which are potent inhibitors of enzymes. DuP-697 and sulindac sulfide were also potent inhibitors of PGHS-2 but both compounds inhibited cellular PGHS-1 activity at higher doses (IC50 = 0.2-0.4 microM). Time-dependent inhibition of PGE2 production in osteosarcoma cells was observed for indomethacin, diclofenac and etodolac. The synthesis of PGE2 by U937 cells was strongly dependent on exogenous arachidonic acid (100-fold stimulation) whereas confluent osteosarcoma cells also produced PGE2 without exogenous stimulus (7-fold stimulation by arachidonic acid). Osteosarcoma cells grown beyond confluence released more PGE2 from endogenous substrate than arachidonic acid stimulated undifferentiated U937 cells. These results indicate that osteosarcoma cells selectively express PGHS-2 with an autocrine regulation and effective utilization of endogenous arachidonic acid for PGE2 synthesis.

Arachidonic Acid↗
PubMed1997

Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor.

1. DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furan one) was identified as a novel orally active and highly selective cyclo-oxygenase-2 (COX-2) inhibitor. 2. In CHO cells stably transfected with human COX isozymes, DFU inhibited the arachidonic acid-dependent production of prostaglandin E2 (PGE2) with at least a 1,000 fold selectivity for COX-2 (IC50 = 41 +/- 14 nM) over COX-1 (IC50 > 50 microM). Indomethacin was a potent inhibitor of both COX-1 (IC50 = 18 +/- 3 nM) and COX-2 (IC50 = 26 +/- 6 nM) under the same assay conditions. The large increase in selectivity of DFU over indomethacin was also observed in COX-1 mediated production of thromboxane B2 (TXB2) by Ca2+ ionophore-challenged human platelets (IC50 > 50 microM and 4.1 +/- 1.7 nM, respectively). 3. DFU caused a time-dependent inhibition of purified recombinant human COX-2 with a Ki, value of 140 +/- 68 microM for the initial reversible binding to enzyme and a kappa 2 value of 0.11 +/- 0.06 s-1 for the first order rate constant for formation of a tightly bound enzyme-inhibitor complex. Comparable values of 62 +/- 26 microM and 0.06 +/- 0.01 s-1, respectively, were obtained for indomethacin. The enzyme-inhibitor complex was found to have a 1:1 stoichiometry and to dissociate only very slowly (t1/2 = 1-3 h) with recovery of intact inhibitor and active enzyme. The time-dependent inhibition by DFU was decreased by co-incubation with arachidonic acid under non-turnover conditions, consistent with reversible competitive inhibition at the COX active site. 4. Inhibition of purified recombinant human COX-1 by DFU was very weak and observed only at low concentrations of substrate (IC50 = 63 +/- 5 microM at 0.1 microM arachidonic acid). In contrast to COX-2, inhibition was time-independent and rapidly reversible. These data are consistent with a reversible competitive inhibition of COX-1. 5. DFU inhibited lipopolysaccharide (LPS)-induced PGE2 production (COX-2) in a human whole blood assay with a potency (IC50 = 0.28 +/- 0.04 microM) similar to indomethacin (IC50 = 0.68 +/- 0.17 microM). In contrast, DFU was at least 500 times less potent (IC50 > 97 microM) than indomethacin at inhibiting coagulation-induced TXB2 production (COX-1) (IC50 = 0.19 +/- 0.02 microM). 6. In a sensitive assay with U937 cell microsomes at a low arachidonic acid concentration (0.1 microM), DFU inhibited COX-1 with an IC50 value of 13 +/- 2 microM as compared to 20 +/- 1 nM for indomethacin. CGP 28238, etodolac and SC-58125 were about 10 times more potent inhibitors of COX-1 than DFU. The order of potency of various inhibitors was diclofenac > indomethacin approximately naproxen > nimesulide approximately meloxicam approximately piroxicam > NS-398 approximately SC-57666 > SC-58125 > CGP 28238 approximately etodolac > L-745,337 > DFU. 7. DFU inhibited dose-dependently both the carrageenan-induced rat paw oedema (ED50 of 1.1 mg kg-1 vs 2.0 mg kg-1 for indomethacin) and hyperalgesia (ED50 of 0.95 mg kg-1 vs 1.5 mg kg-1 for indomethacin). The compound was also effective at reversing LPS-induced pyrexia in rats (ED50 = 0.76 mg kg-1 vs 1.1 mg kg-1 for indomethacin). 8. In a sensitive model in which 51Cr faecal excretion was used to assess the integrity of the gastrointestinal tract in rats, no significant effect was detected after oral administration of DFU (100 mg kg-1, b.i.d.) for 5 days, whereas chromium leakage was observed with lower doses of diclofenac (3 mg kg-1), meloxicam (3 mg kg-1) or etodolac (10-30 mg kg-1). A 5 day administration of DFU in squirrel monkeys (100 mg kg-1) did not affect chromium leakage in contrast to diclofenac (1 mg kg-1) or naproxen (5 mg kg-1). 9. The results indicate that COX-1 inhibitory effects can be detected for all selective COX-2 inhibitors tested by use of a sensitive assay at low substrate concentration. The novel inhibitor DFU shows the lowest inhibitory potency against COX-1, a consistent high selectivity of inhibition of COX-2 over COX-1 (>300 fold) with enzyme, whole cell and whole blood assays, with no detectable loss of integrity of the gastrointestinal tract at doses >200 fold higher than efficacious doses in models of inflammation, pyresis and hyperalgesia. These results provide further evidence that prostanoids derived from COX-1 activity are not important in acute inflammatory responses and that a high therapeutic index of anti-inflammatory effect to gastropathy can be achieved with a selective COX-2 inhibitor.

Administration, Oral↗
PubMed1997

Seroprevalence of and risk factors for hepatitis A infection among young homosexual and bisexual men.

To evaluate hepatitis A infection among young homosexual and bisexual men, 411 men aged 17-22 years were surveyed at 26 public venues in San Francisco and Berkeley. Seroprevalence of hepatitis A infection was 28.0% (95% confidence interval [CI], 23.7%-32.6%). Recent infection was evident in 3.3% of susceptible men (95% CI, 1.6%-5.9%). Independent predictors of hepatitis A infection were Latino ethnicity (odds ratio [OR] = 5.3; 95% CI, 3.1-8.9), having > or = 50 lifetime male sex partners (OR = 1.8; 95% CI, 1.1-3.0), less than high school education (OR = 2.2; 95% CI, 1.2-4.1), and being a high school graduate (OR = 1.7; 95% CI, 1.0-2.9). Independent predictors of recent infection were less than high school graduate (OR = 7.6; 95% CI, 1.9-30.5), insertive anal intercourse (OR = 5.6; 95% CI, 1.0-32.8), and sharing needles without cleaning them (OR = 32.1; 95% CI, 3.0-346). Hepatitis A is a common infection in young homosexual men and is associated with sexual and drug-using behaviors.

Adolescent↗
PubMed1997

Lateral electron transport in FFT photon dose calculations.

Previously published FFT dose calculations and their verifications have been performed for field sizes greater than 10 cm x 10 cm with photon energies up to 18 MV [Zhu and Boyer, Phys. Med. Biol. 35, 351-368 (1990)]. With a smaller field size at megavoltage energies, lateral electronic disequilibrium exists in low density inhomogeneities which is not handled properly by the FFT calculations. In this paper, we extend FFT dose calculations to address this problem without significantly increasing the computational time. We employ lateral scaling of the field size at each depth along with an inverse scaling of the resultant dose distribution. The concept of effective density in introduced for the lateral and inverse scaling. We demonstrate that electron transport can be adequately captured in the presence of inhomogeneities, thus improving 3D FFT dose calculations in inhomogeneous media.

Calibration↗
PubMed1997

Determinants of peak bone mass in Chinese women aged 21-40 years. III. Physical activity and bone mineral density.

Previous studies on the relation between moderate physical activity and bone mass have observed conflicting results. Many of these studies have not dissociated the role of physical activity by age groups and in relation to the period of peak bone mass formation. Our cross-sectional analysis of the baseline data of a longitudinal study of 273 women aged 21-40 attempted to evaluate the role of moderate physical activity on bone mass around the period of peak bone mass attainment. The analyses were carried out separately for the two age groups--21-30 and 31-40--and had also taken into account the effects of age, dietary calcium intake, and lean body mass on bone mineral density (BMD). The total metabolic equivalent values (MET) of leisure time physical activity was based on the MET values for each activity and the reported time spent on each activity in the past year. The results indicated that among the younger group of women, high level of leisure time physical activity was associated with higher bone mass at both the spine and the hip. Additive effects of physical activity and dietary calcium intake on the spine and the hip BMD were observed. Together with age and lean body mass, physical activity and dietary calcium intake accounted for 19% of the variances of bone mineral at the spine and 9-11% at the hip. Among women aged 31-40, presumably after the peak bone mass formation, lean body mass as well as fat mass have independent strong association with BMD. Physical activity was not associated with bone mass in this age group.

Absorptiometry, Photon↗
PubMed1997

New roller pump disposable provides safety and simplifies occlusion setting.

A new disposable insert for the arterial roller pump, the Better-Header, provides safety and functionality beyond what standard tubing provides. It automatically limits pump outlet pressure to a level determined by the user and provides a self-contained, simple means to set pump occlusion. The Better-Header consists of a Starling-like pressure relief valve connected across standard header tubing. As long as arterial line pressure at the pump outlet remains below a set limit, the valve is closed. If line pressure approaches the pressure limit, the valve opens, preventing overpressurization by shunting blood from pump outlet to inlet. The Better-Header can also be used to set occlusion by the "dynamic method" to obtain nonocclusive settings. The Better-Header was evaluated in the lab for its pressure-flow characteristics. Even when the arterial line was completely clamped at a pump flow of 7 L/min, line pressure was limited to a safe level and all circuit connections were preserved. The Better-Header has been used successfully at North Shore University Hospital in over 500 clinical cases covering a wide range of patients and procedures. In several instances, the user was alerted to high pressure situations by fluid flow through the valve and by an audible alarm, allowing rapid correction of the source of pressure. Compared to the standard setup, the Better-Header maintains outlet pressure within safe, user-settable limits, and permits consistent, nonocclusive settings with predictable retrograde flow.

Adolescent↗
PubMed1997

Comparison of the cyclooxygenase-1 inhibitory properties of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors, using sensitive microsomal and platelet assays.

Two forms of cyclooxygenase (COX) activity are involved in the synthesis of prostaglandins, prostacyclins, and thromboxanes in mammalian cells. There is now convincing evidence, obtained with a number of structurally distinct inhibitors, that selective COX-2 inhibitors possess anti-inflammatory effects with an improved gastrointestinal tolerability compared with conventional nonsteroidal anti-inflammatory drugs (NSAIDs) affecting both COX-1 and COX-2. As more selective COX-2 inhibitors are being developed, assays with a high degree of sensitivity to inhibition are needed to compare the relative effects of compounds on COX-1 activity. In the present report, we describe a sensitive assay for the inhibition of human COX-1 based on the production of prostaglandin E2 by microsomes from U937 cells incubated with a subsaturating concentration of arachidonic acid. More than 45 NSAIDs and selective COX-2 inhibitors were tested in this assay. IC50 values ranged from 1 nM for flunixin and flurbiprofen to about 200-500 microM for salicylate and acetaminophen. Potent and nonselective NSAIDs such as sulindac sulfide, diclofenac, and indomethacin showed IC50 values of < 20 nM. Among the compounds that have been reported to show selectivity for COX-2, the rank order of potency against COX-1 was DuP 697 > SC-58451 > celecoxib > nimesulide-meloxicam-piroxicam-NS-398-RS-57067 > SC-57666 > SC-58125 > flosulide > etodolac > L-745,337 > DFU-T-614, with IC50 values ranging from 7 nM to 17 microM. A good correlation was obtained between the IC50 values for the inhibition of microsomal COX-1 and both the inhibition of TXB2 production by Ca2+ ionophore challenged platelets and the inhibition of prostaglandin E2 production by CHO cells stably expressing human COX-1. However, the microsomal assay was more sensitive to inhibition than cell-based assays and allowed the detection of inhibitory effects on COX-1 for all NSAIDs and selective COX-2 inhibitors examined with discrimination of their potency under conditions of limited availability of arachidonic acid.

Animals↗