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Biomedical subjects

W Yuan

Publications and source records attributed to W Yuan.

At least 73 records · Page 4Linked to original sources

Effects of prediction on timing and dynamics of vergence eye movements.

Periodic square waves were used to generate predictable vergence eye movement responses. The timing and dynamic characteristics of vergence eye movement responses to predictable and non-predictable stimuli were compared. Results showed significant changes in timing characteristics along with a highly characteristic anticipatory movement in the early part of predictable vergence responses. This phenomenon is similar to that seen in saccadic eye movements and appears to influence the timing and dynamics of the subsequent vergence response. A model-based analysis of dynamics showed that the pulse width, pulse gain, and step gain of the motor command signal did not show major differences between predictable and non-predictable response. However, other model parameters related to the acceleration of the response showed a substantial decrease when the movements were predictive.

Eye Movements↗

Relationship between serum or tissue ouabain and blood pressure in 1k1c hypertensive rats.

OBJECTIVE: To evaluate the role of endogenous ouabain (EO) in the development of hypertension and the characteristics of EO secretion in 1k1c (one kidney, one clipped) hypertensive rats. METHODS: EO content of serum and tissues in 1k1c hypertensive rats and normal control Sprague-Dawley (SD) rats was detected by the method of enzyme linked immunosorbent assay (ELISA). The relationship between serum or tissue ouabain and blood pressure was analyzed in 1k1c hypertensive rats. RESULTS: The ouabain content of serum, heart, kidney, adrenal gland, pituitary and hypothalamus was significantly higher in 1k1c hypertensive rats than that in normal control SD rats (2.25, 2.63, 3.35, 40.37, 3.34, 15.7 micrograms/kg tissue in 1k1c hypertensive rats vs 1.12, 1.79, 1.73, 27.54, 1.83, 10.10 micrograms/kg tissue in control SD rats, respectively. P < 0.05 for all of these comparisons). The ouabain content of the adrenal gland and the hypothalamus was higher than that of other tissues or serum, both in 1k1c rats and in control SD rats. The EO content of serum, kidney and hypothalamus was significantly correlated with blood pressure in 1k1c hypertensive rats (r = 0.59, 0.63, 0.52, respectively. P < 0.05). The ouabain content of heart, liver, adrenal gland and pituitary was not correlated with blood pressure. CONCLUSIONS: EO might play an important role in the development of hypertension in 1k1c hypertensive rats. The adrenal gland may be a major source of EO and the hypothalamus-pituitary-adrenal axis may be involved in the regulation of EO secretion.

Animals↗

[Study of congenital velopharyngeal insufficiency and hypernasality].

OBJECTIVE: To evaluate 27 congenital veloparyngeal insufficiency(CVPI) subjects and 6 normal articulation subjects with airflow pressure techniques. METHODS: A compare analysis was performed in two groups (CVPI subjects and normal articulation subjects) during speech production of /hemper/ and /papa/. RESULTS: There wasn't statistical significance between two groups in oral air pressure and velopharyngeal orifice areas, however, CVPI group differed significant in nasal airflow on the articulation of /hemper/ and /papa/. CONCLUSIONS: When the degree of CVPI subject's VP opening was small, hypernasality appeared to be related to duration of the opening-closing movements.

Adolescent↗

[Anterior corpectomy combined with cervical spine locking plate for treatment of multilevel cervical spondylotic myelopathy].

OBJECTIVE: To study the value of cervical spine locking plate (CSLP) combined with anterior corpectomy in treating multilevel cervical spondylotic myelopathy (CSM). METHODS: In 55 CSM patients, 36 were male and 19 female, aged on average 51.5 years. The duration of illness was 13 months on average. Pathological segments in 47 patients included two functional segments and in 8 three functional segments. All patients were treated with anterior corpectomy and self-iliac bone graft and CSLP fixation. RESULTS: 51 patients were followed up for 26 months on average. All grafting bones got solid fusion in 12 to 16 weeks postoperatively. Intervertebral spaces were restored after operation. The physiological curve of the cervical spine was good. The effective rate of operation was 94.1% (48/51) and the excellent rate 78.4% (40/51). The JOA score rose from 8.3 points before operation to 14.1 points after operation. CONCLUSIONS: Anterior corpectomy and osteosynthesis of multilevel cervical spondylotic myelopathy are indicated for CSLP fixation. CSLP in the treatment of cervical spine instability is prospective.

Aged↗

[The recognition of the epidemic area of tsutsugamushi disease on Nan Peng Lie Island in China and the strategy of prevention].

OBJECTIVE: To investigate the region for the epidemic area of tsutsugamushi disease. METHODS: Epidemiological studies, Orientia tsutsugamushi isolation, and preventive measures were used. RESULTS: The region belonged to epidemic area of south subtropical zone. The main host was found Rattus norvegicu. The main biological vector was Leptotrombidium deliens. The seasonal trends of the quantity of Rattus norvegicu and Leptotrombidium deliens were consistent with the incidence change of the disease in the region. Orientia tsutsugamushi has been isolated from Rattus norvegicu and Leptotrombidium deliens. Data showed that Orientia tsutsugamushi isolated strains mainly belongs to Karp. Sero-epidemiological data showed that antibodies of Orientia tsutsugamushi are 100.0% positive in the residents of the region and 4.0% in army men. After taking comprehensive preventive measures, the incidence was descending. CONCLUSION: Nan Peng Lie island was proved an epidemic area of tsutsugamushi disease.

Animals↗

[Effects of maxillary growth of Wistar rats with bilateral artificial cleft palate after premaxillary orthopedic treatment on expression of proliferating cell nuclear antigen(PCNA)].

OBJECTIVE: Being based on the principle of Latham's appliance, this experiment is designed to detect activity of osteoblasts in the maxillary sutures of Wistar rats with bilateral artificial cleft palate by immunohistochemistry technique, and evaluate the effects of this appliance on the growth and development of the maxilla. METHODS: The animal models of male infant Wistar rats with bilateral cleft palate were made by removing some palatal bones, splitting a "V" gap of 1.5 cm wide at the line between premaxilla and segments of maxilla. A sort of appliances, which could be fixed in the mouth of Wistar rats with bilateral cleft palate for correcting protrusion premaxilla was constructed basing on the principle of Latham's appliance. Then the diferent pathological changes of osteoblast proliferation between the experimental group and the two controlled groups were examined. The jugomaxillary sutrues, temporomalar sutures and sphenoipalatine suture were harvested 7, 14 days after premaxillar orthopedic treatment, followed by 4% paraformaldehyde fixing about 1 hour, demineralization with 15% EDTA and 0.5% paraformaldehyde for 48 hours, distilled water washing for a night, dimethylbenzene transparant dealing, and paraffin wax embeding. Proliferating Osteoblasts in all these sutures were investigated using immunohiostochemical technique with monoclonal antibodies of proliferating cell nuclear antigen (PCNA). RESULTS: Seven days after orthopedic treatment, no significant difference was observed between the experimental group and the two controlled groups. While after fourteen days, obvious PCNA-positive expression were observed in cells of all these sutures of the experimental group. CONCLUSION: The distribution of proliferating cells and the degree of cell proliferation change after premaxillary orthopedic treatment. And significant cell proliferation is observed in the experimental group, but there are no significant differences between the two controlled groups.

Animals↗

[Analysis of maxillary dental-arch dimensions in adult unoperated cleft palate patients].

OBJECTIVE: Analysis of maxillary dental-arch development in adult unoperated cleft palate patients. METHODS: Dental casts was studied in 20 cases of adult unoperated cleft palate (UCP) patients, and 20 cases of normal adults were as a control group. RESULTS: The UCP group showed smaller dental-arch widths than a control group in the canine region (P < 0.05) and these was no significant difference on upper-arch depth and posterior dental arch widths between the UCP group and a control group (P > 0.05). CONCLUSION: In the UCP group major deformity were in incisor and canine region, and smaller interfere to posterior dental-arch widths and depth. Operation for cleft lip can interfere maxillary dental-arch development.

Adolescent↗

[Cephalometrical analysis of effects of premaxillary orthopedic treatment on maxillary growth of Wistar rats with bilateral artificial cleft palate].

OBJECTIVE: To measure the differences between the experimental group and the two controlled groups by using the cephalometric radiography technique to study the effects of premaxillary orthopedic treatments on the growth and development of maxilla. METHODS: To make an animal model with bilateral cleft palate by surgery operation: General anesthesia was carried on by injecting 2.5% pentobarbital (25 mg/kg) into abdominal cavity, then almost the same bone of rats' palate were removed from bilateral palate. An appliance, based on the principle of Latham's appliance was made and designed for premaxillary orthopedic treatment. It was fixed in rats' palate using pins under the condition of general anesthesia. After 20 days of orthopedic treatment, the rats were anesthetized by ether, and cephalometric films were taken under self-designed cephalometer and analysed aided by computer. RESULTS: The distances that represented the maxillary position in the posterior-anterior (PA) direction significantly increased (P < 0.05), while the angles that represented the direction of premaxillary growth significantly decreased (P < 0.05) between the experimental group and the two controlled groups. There were no significant difference between the two controlled groups. CONCLUSION: Premaxilla of rats can be effectively moved backward and rotated downward and backward on the PA direction by appliance. The appliance can move the segment palate forward during the premaxillary backword. The appliance can stimulate maxillary growth.

Animals↗

Evaporation of Accretion Disks around Black Holes: The Disk-Corona Transition and the Connection to the Advection-dominated Accretion Flow.

We apply the disk-corona evaporation model (Meyer & Meyer-Hofmeister) originally derived for dwarf novae to black hole systems. This model describes the transition of a thin cool outer disk to a hot coronal flow. The mass accretion rate determines the location of this transition. For a number of well-studied black hole binaries, we take the mass flow rates derived from a fit of the advection-dominated accretion flow (ADAF) model to the observed spectra (for a review, see Narayan, Mahadevan, & Quataert) and determine where the transition of accretion via a cool disk to a coronal flow/ADAF would be located for these rates. We compare this with the observed location of the inner disk edge, as estimated from the maximum velocity of the Halpha emission line. We find that the transition caused by evaporation agrees with this determination in stellar disks. We also show that the ADAF and the "thin outer disk + corona" are compatible in terms of the physics in the transition region.

Journal Article↗

Cryphonectria hypovirus 3, a virus species in the family hypoviridae with a single open reading frame.

Isolate Grand Haven (GH) 2 is a naturally occurring isolate of the chestnut blight fungus, Cryphonectria parasitica, that is greatly reduced in virulence due to the presence of a double-stranded RNA virus. Unlike many other virus-infected, hypovirulent isolates, GH2 is not substantially reduced in pigmentation, conidiation, or laccase expression compared to its virus-free counterpart. The dsRNA genome of the GH2 virus was cloned, sequenced, and compared to hypovirulence-associated viruses of the family Hypoviridae. GH2 dsRNA is considerably smaller than previously characterized members of the family, 9.8 kb compared to 12.5-12.7 kb for other members. The genome organization of GH2 dsRNA reflected the substantial difference in genome size. Like other members of the family, one strand contained a poly(A)(+) tail at the 3' end and a long sequence with several minicistrons at the 5' end of the same strand. Only a single open reading frame (ORF) of 8622 nucleotides was predicted from deduced translations of the poly(A)(+)-containing strand, however. This contrasts with the two-ORF structures of previously characterized members. Analysis of the deduced ORF of GH2 dsRNA revealed putative proteinase, RNA polymerase, and helicase domains similar to those previously identified in confirmed members of the virus family Hypoviridae. GH2 dsRNA was more distantly related to Cryphonectria hypovirus (CHV) 1-EP713 and CHV2-NB58 than the latter two were to each other but has features in common with each of those viruses. We propose that the GH2 virus be included in this taxon as a member of the genus Hypovirus, representing a strain of a new species, CHV3.

Amino Acid Sequence↗

Mapping ligand binding domains in chimeric fibroblast growth factor receptor molecules. Multiple regions determine ligand binding specificity.

Fibroblast growth factors (FGFs) mediate essential cellular functions by activating one of four alternatively spliced FGF receptors (FGFRs). To determine the mechanism regulating ligand binding affinity and specificity, soluble FGFR1 and FGFR3 binding domains were compared for activity. FGFR1 bound well to FGF2 but poorly to FGF8 and FGF9. In contrast, FGFR3 bound well to FGF8 and FGF9 but poorly to FGF2. The differential ligand binding specificity of these two receptors was exploited to map specific ligand binding regions in mutant and chimeric receptor molecules. Deletion of immunoglobulin-like (Ig) domain I did not effect ligand binding, thus localizing the binding region(s) to the distal two Ig domains. Mapping studies identified two regions that contribute to FGF binding. Additionally, FGF2 binding showed positive cooperativity, suggesting the presence of two binding sites on a single FGFR or two interacting sites on an FGFR dimer. Analysis of FGF8 and FGF9 binding to chimeric receptors showed that a broad region spanning Ig domain II and sequences further N-terminal determines binding specificity for these ligands. These data demonstrate that multiple regions of the FGFR regulate ligand binding specificity and that these regions are distinct with respect to different members of the FGF family.

Amino Acid Sequence↗

Upregulation of Na(+)/Ca(2+) exchanger expression and function in an arrhythmogenic rabbit model of heart failure.

Three-dimensional cardiac mapping in rabbits with nonischemic cardiomyopathy has shown that ventricular arrhythmias initiate by a nonreentrant mechanism that may be due to triggered activity from delayed afterdepolarizations. Delayed afterdepolarizations are thought to be due to spontaneous release of Ca(2+) from the sarcoplasmic reticulum (SR) and consequent activation of an inward Na(+)/Ca(2+) exchange (NaCaX) current. The goal of this study was to determine whether there is enhanced NaCaX gene expression and functional activity that may contribute to nonreentrant activation. Heart failure (HF) was induced in rabbits by combined aortic insufficiency and aortic constriction. HF rabbits had left ventricular enlargement (left ventricular end-diastolic dimension increased from 1.43+/-0.03 to 1.97+/-0.05 cm) and severely depressed function (fractional shortening reduced from 37% to 26%, P<0.02). Heart-to-body weight was increased by 79% in HF. Western blots showed a 93% increase in NaCaX protein in HF (P<0.04). NaCaX mRNA (7-kb transcript) was increased by 104% relative to the 18S rRNA in HF. A 14-kb NaCaX transcript was also seen in the HF rabbits, raising total NaCaX mRNA to 2.7-fold compared with controls. The amplitude of caffeine-induced contractures, used to assess SR Ca(2+) load, was not significantly different in HF. Relaxation and [Ca(2+)](i) decline during caffeine-induced contractures is attributable to Ca(2+) transport by NaCaX and was 61% and 45% faster in HF (P<0.05), respectively. NaCaX current measured under controlled voltage clamp conditions was also 2-fold higher in HF cells. SR Ca(2+)-ATPase mRNA and protein levels and Ca(2+) current density were not significantly altered in HF. Twitch amplitudes from HF myocytes were 26% smaller compared with control (P<0.02), but twitch relaxation and [Ca(2+)](i) decline (due largely to SR Ca(2+)-ATPase) were not altered. Thus myocytes and myocardium from HF rabbits exhibit enhanced NaCaX expression and function. The enhanced NaCaX activity may contribute to depressed contractions, increased transient inward current (for a given SR Ca(2+) release), delayed afterdepolarizations, and nonreentrant initiation of ventricular tachycardia in this arrhythmogenic model of HF.

Animals↗

Ca(2+) influx through Ca(2+) channels in rabbit ventricular myocytes during action potential clamp: influence of temperature.

Ca(2+) influx via Ca(2+) current (I(Ca)) during the action potential (AP) was determined at 25 degrees C and 35 degrees C in isolated rabbit ventricular myocytes using AP clamp. Contaminating currents through Na(+) and K(+) channels were eliminated by using Na(+)- and K(+)-free solutions, respectively. DIDS (0.2 mmol/L) was used to block Ca(2+)-activated chloride current (I(Cl(Ca))). When the sarcoplasmic reticulum (SR) was depleted of Ca(2+) by preexposure to 10 mmol/L caffeine, total Ca(2+) entry via I(Ca) during the AP was approximately 12 micromol/L cytosol (at both 25 degrees C and 35 degrees C). Similar Ca(2+) influx at 35 degrees C and 25 degrees C resulted from a combination of higher and faster peak I(Ca), offset by more rapid I(Ca) inactivation at 35 degrees C. During repeated AP clamps, the SR gradually fills with Ca(2+), and consequent SR Ca(2+) release accelerates I(Ca) inactivation during the AP. During APs and contractions in steady state, total Ca(2+) influx via I(Ca) was reduced by approximately 50% but was again unaltered by temperature (5.6+/-0.2 micromol/L cytosol at 25 degrees C, 6.0+/-0.2 micromol/L cytosol at 35 degrees C). Thus, SR Ca(2+) release is responsible for sufficient I(Ca) inactivation to cut total Ca(2+) influx in half. However, because of the kinetic differences in I(Ca), the amount of Ca(2+) influx during the first 10 ms, which presumably triggers SR Ca(2+) release, is much greater at 35 degrees C. I(Ca) during a first pulse, given just after the SR was emptied with caffeine, was subtracted from I(Ca) during each of 9 subsequent pulses, which loaded the SR. These difference currents reflect I(Ca) inactivation due to SR Ca(2+) release and thus indicate the time course of local [Ca(2+)] in the subsarcolemmal space near Ca(2+) channels produced by SR Ca(2+) release (eg, maximal at 20 ms after the AP activation at 35 degrees C). Furthermore, the rate of change of this difference current may reflect the rate of SR Ca(2+) release as sensed by L-type Ca(2+) channels. These results suggest that peak SR Ca(2+) release occurs within 2.5 or 5 ms of AP upstroke at 35 degrees C and 25 degrees C, respectively. I(Cl(Ca)) might also indicate local [Ca(2+)], and at 35 degrees C in the absence of DIDS (when I(Cl(Ca)) is prominent), peak I(Cl(Ca)) also occurred at a time comparable to the peak I(Ca) difference current. We conclude that SR Ca(2+) release decreases the Ca(2+) influx during the AP by approximately 50% (at both 25 degrees C and 35 degrees C) and that changes in I(Ca) (and I(Cl(Ca))), which depend on SR Ca(2+) release, provide information about local subsarcolemmal [Ca(2+)].

Action Potentials↗

The mouse SLIT family: secreted ligands for ROBO expressed in patterns that suggest a role in morphogenesis and axon guidance.

The Slit gene encodes a secreted molecule essential for neural development in Drosophila embryos. Here we report the identification of three Slit homologues in the mouse. We demonstrate that the mouse SLIT1 protein can bind ROBO1, a transmembrane receptor implicated in axon guidance. Both whole-mount and section in situ hybridization studies reveal unique and complementary patterns of expression of the three mouse Slit genes and of Robo1, both within the central nervous system and in other developing tissues. The complementary expression patterns of Slit and Robo1 and their in vitro interaction suggest a ligand-receptor relationship. The expression of all three Slit genes in the floor plate suggests that they are likely to share the same functional properties with their Drosophila homologue in midline neural development and axon guidance. The complementary expression of Slit and Robo1 in different subdivisions of the somites suggests their possible function in axon pathfinding and neural crest cell migration. The unique expression pattern in limb and other organs indicates additional potential functions of the Slit gene family.

Amino Acid Sequence↗

Vertebrate slit, a secreted ligand for the transmembrane protein roundabout, is a repellent for olfactory bulb axons.

The olfactory bulb plays a central role in olfactory information processing through its connections with both peripheral and cortical structures. Axons projecting from the olfactory bulb to the telencephalon are guided by a repulsive activity in the septum. The molecular nature of the repellent is not known. We report here the isolation of vertebrate homologs of the Drosophila slit gene and show that Slit protein binds to the transmembrane protein Roundabout (Robo). Slit is expressed in the septum whereas Robo is expressed in the olfactory bulb. Functionally, Slit acts as a chemorepellent for olfactory bulb axons. These results establish a ligand-receptor relationship between two molecules important for neural development, suggest a role for Slit in olfactory bulb axon guidance, and reveal the existence of a new family of axon guidance molecules.

Animals↗

Rapid effects of corticosterone on cardiovascular neurons in the rostral ventrolateral medulla of rats.

The present study has explored possible fast actions of corticosteroid hormones on activity of cardiovascular neurons of the rostral ventrolateral medulla. Experiments were conducted in 60 urethane-anesthetized, artificially ventilated adult rats. Extracellular recordings of unitary firings were made from the RVLM with multi- or single-barreled microelectrodes. Barosensitive cardiovascular neurons were identified through activation of the baroreceptor reflex by electrical stimulation of the aortic nerve and by intravenous injection of phenylephrine. In 52 barosensitive cardiovascular neurons, iontophoretically applied corticosterone sulfate increased the ongoing activity of 30 (57.7%) neurons, the other 22 (42.3%) neurons being unaffected. In 16 bulbospinal pre-sympathetic neurons, iontophorized corticosterone increased the firing rate of 12 neurons. Intravenously applied corticosterone (0.2 mg) increased the firing rates of 5 out of 12 bulbospinal pre-sympathetic neurons. The average baseline activity of cardiovascular neurons sensitive to corticosterone was found to be significantly less than that of the cardiovascular neurons insensitive to corticosterone. In 64 non-cardiovascular neurons, the firing rate of 13 (20.3%) neurons increased, 23 (36.0%) decreased and 28 (43.7%) remained unchanged following local application of corticosterone. The changes in firing rates of RVLM neurons following application of corticosterone occurred rapidly and were dependent on the doses of the agent. RU-38486 was able to reduce or block the rapid effects of corticosterone on cardiovascular and non-cardiovascular neurons. The results demonstrated that corticosterone may fast, non-genomically, modulate the activity of central regulators of the cardiovascular system and suggested that fast non-genomic actions of corticosteroid hormones may be an important mechanism in the integration of the autonomic nervous and the cardiovascular systems during some conditions such as stress.

Action Potentials↗

Negative modulation of alpha1(I) procollagen gene expression in human skin fibroblasts: transcriptional inhibition by interferon-gamma.

Interferon-gamma (IFN-gamma), a multifunctional cytokine produced by activated Th1 lymphocytes, exerts potent effects on the extracellular matrix by regulating fibroblast function. In this study, we examined the modulation of alpha1(I) procollagen gene (COL1A1) expression by recombinant IFN-gamma. The results showed that IFN-gamma stimulated the rapid accumulation of interferon regulated factor (IRF)-1 mRNA, followed by a delayed and dose-dependent inhibition of alpha1(I) procollagen mRNA expression in skin fibroblasts from several different donors. The inhibitory response was abrogated in fibroblasts stably expressing IRF-1 in the antisense orientation. A marked decrease in the amount of heterogeneous nuclear pre-mRNA preceded the inhibition of COL1A1 mRNA expression. In fibroblasts transiently transfected with COL1A1 promoter-chloramphenicol acetyltransferase reporter gene plasmids, IFN-gamma selectively inhibited promoter activity and abrogated its stimulation induced by TGF-beta. The inhibition by IFN-gamma was not due to downregulation of TGF-beta receptor mRNA expression in the fibroblasts or decreased ligand binding to the receptor. IFN-alpha and IFN-beta by themselves had little effect on promoter activity, but IFN-alpha augmented the inhibitory effect of IFN-gamma. Using a series of 5' deletion constructs, a proximal region of the COL1A1 promoter was shown to function as an IFN-gamma response element. This region of the gene harbors overlapping binding sites for transcription factors Sp1, Sp3, and NF-1 but no homologs of previously characterized IFN-gamma response elements. The putative IFN-gamma response region was sufficient to confer inhibition of reporter gene expression by treatment with IFN-gamma. Gel mobility shift analysis showed that two distinct and specific DNA-protein complexes were formed when fibroblast nuclear extracts were incubated with oligonucleotides spanning the IFN-gamma response region. IFN-gamma did not modify the ability of nuclear proteins to bind to this region. The results indicate that IFN-gamma inhibits COL1A1 expression in fibroblasts principally at the level of gene transcription. Inhibition involves IRF-1 and is mediated through a short proximal promoter segment but without an apparent change in promoter occupancy. The findings provide novel insight into the mechanism of IFN-gamma regulation of fibroblast function.

Adult↗

Characterization of rofecoxib as a cyclooxygenase-2 isoform inhibitor and demonstration of analgesia in the dental pain model.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and indomethacin (INN, indometacin) inhibit both the constitutive (COX-1) and inducible (COX-2) isoforms of cyclooxygenase. The induction of COX-2 after inflammatory stimuli has led to the hypothesis that COX-2 inhibition primarily accounts for the therapeutic properties of NSAIDs. METHODS: Chinese hamster ovary (CHO) cell lines that express each COX isoform were used to characterize the in vitro selectivity of rofecoxib. Single oral doses of rofecoxib and indomethacin were then assessed in subjects with use of ex vivo COX-isoform specific assays (serum thromboxane B2 [TXB2] and lipopolysaccharide [LPS]-stimulated whole blood prostaglandin E2 and assays of COX-1 and COX-2 activity, respectively). A double-blind, parallel-group study compared the analgesic efficacy of rofecoxib to placebo and ibuprofen in 102 patients with dental pain. RESULTS: Rofecoxib showed a >800-fold COX-2 selectivity with use of CHO cells that express human COX-1 and COX-2. In subjects, dose- and concentration-dependent inhibition of LPS-stimulated prostaglandin E2 was observed with both rofecoxib (IC50 [the concentration estimated to produce 50% inhibition], 0.77 micromol/L) and indomethacin (IC50, 0.33 micromol/L). Whereas indomethacin inhibited TXB2, (IC50, 0.14 micromol/L), no inhibition was observed with rofecoxib even at doses of up to 1000 mg. In the dental pain study, total pain relief (TOTPAR) over the 6 hours after dosing was similar between 50 mg and 500 mg rofecoxib and 400 mg ibuprofen (P > .20). All active treatments showed greater improvement than placebo (P < .001) CONCLUSIONS: Rofecoxib inhibited COX-2 without evidence of COX-1 inhibition, even at oral doses of up to 1000 mg. Nonetheless, rofecoxib showed analgesic activity indistinguishable from that observed with ibuprofen, a nonisoform-selective COX inhibitor. These results support the hypothesis that the analgesic effects of NSAIDs primarily derive from inhibition of COX-2.

Adult↗