Biomedical subjects

A Appel

Publications and source records attributed to A Appel.

At least 19 recordsLinked to original sources

PubMed2001

A randomized trial of a dissonance-based eating disorder prevention program.

OBJECTIVE: As psychoeducational eating disorder prevention programs have not been shown to reduce bulimic pathology, we developed and evaluated a dissonance-based intervention for high-risk populations. METHOD: Young women (N = 87) with body image concerns were randomized to this intervention, which involves verbal, written, and behavioral exercises requiring them to critique the thin-ideal, or to a healthy weight management control group. Participants completed a baseline, termination, and 4-week follow-up survey. RESULTS: Participants in the dissonance intervention reported decreased thin-ideal internalization, body dissatisfaction, dieting, negative affect, and bulimic symptoms at termination and at 4-week follow-up. Unexpectedly, participants in the healthy weight management control group also reported some benefits. DISCUSSION: Taken in conjunction with past findings, these preliminary results suggest that the dissonance intervention, and to a lesser extent the healthy weight management intervention, may reduce bulimic pathology and risk factors for eating disturbances.

Adolescent↗

PubMed1999

Conventional and extended-release etodolac for postsurgical dental pain.

This double-masked, parallel-group, randomized study compared the analgesic efficacy and tolerability of a single investigational 1200-mg dose of extended-release etodolac with those of a single 400-mg dose of extended-release etodolac and twice-daily doses of conventional etodolac 200 and 400 mg and placebo given 8 hours apart in 237 patients with moderate or severe postoperative pain following surgical removal of > or = 2 impacted third molars. Both doses of conventional etodolac and the 1200-mg dose of extended-release etodolac were significantly more effective on all summary analgesic measures than placebo (P < 0.05). Conventional etodolac had an onset of analgesic activity within 45 (400 mg) to 60 (200 mg) minutes and an analgesic duration of 5 to 6 hours. Extended-release etodolac 1200 mg had an onset of action within 60 minutes and an analgesic duration of 12 to 24 hours. At hours 2 and 3, conventional etodolac 400 mg was significantly more effective than the other treatments; from hours 6 through 12, extended-release etodolac 1200 mg was significantly more effective than the other treatments (both, P < 0.05). No serious adverse events were observed in this study, with an incidence of side effects in the active etodolac groups no different than that with placebo. Extended-release etodolac 1200 mg has a prolonged analgesic duration and an acceptable side-effect profile in the oral surgery pain model.

Adult↗

PubMed1999

Molecular mechanisms of T lymphocyte activation: convergence of T cell antigen receptor and IL-1 receptor-induced signaling at the level of IL-2 gene transcription.

Co-stimulation of murine EL-4 thymoma cells-carrying high numbers of TCR and type I IL-1 receptors (IL-1R)-with anti-CD3 antibodies and IL-1 resulted in synergistic enhancement of IL-2 synthesis. While the extracellular signal-regulated kinase (ERK) cascade was activated by both receptors, IL-1 preferentially stimulated Jun-N-terminal kinases (JNK) and p38 mitogen-activated kinase or microtubule-associated protein kinase (MAPK). Interruption of TCR- or IL-1R-stimulated ERK cascade by PD-98059, a specific inhibitor of MAP/ERK kinase (MEK), resulted in partial suppression of nuclear factor of activated T cells activation and in complete inhibition of IL-1-stimulated NFkappaB activation. Suppression of activation of both MEK and p38 MAPK resulted in significant inhibition of IL-2 gene expression. The results show that maximal activation of the IL-2 gene requires activation of at least two different protein kinase cascades, i.e. of the ERK and p38 pathways but presumably also that of JNK which converge at the level of the IL-2 promoter resulting in enhancement of its transcriptional activity.

Animals↗

PubMed1999

Pharmacokinetic and pharmacodynamic action of etodolac in patients after oral surgery.

The objective of this double-blind, randomized, parallel-group study was to evaluate the pharmacokinetics of etodolac and the pharmacodynamic response of pain in patients following oral surgery who had received 200 or 400 mg of etodolac immediate release (IR), 400 or 1200 mg of etodolac extended release (ER), or a placebo. Etodolac concentrations in 441 plasma samples from 187 patients were analyzed for population pharmacokinetics using the NONMEM program. A one-compartment pharmacokinetic model with first-order absorption described the observed data. For etodolac IR, the population mean (%CV) estimates were 3.01 L/h (5.3%) for clearance, 13.6 L (6.8%) for volume of distribution, and 2.31 h-1 (33%) for ka. Respective values for etodolac ER were 3.68 L/h (11%) for clearance, 24.3 L (22%) for volume of distribution, and 0.172 h-1 (24%) for ka. These values generally agreed with previously reported values in healthy adults. Pharmacodynamic assessments included collection of a four-level categorical rating of pain intensity for up to 24 hours after treatment. Pain intensity difference scores were temporally related to etodolac concentrations and were described using an indirect response model. Mean (%CV) pharmacodynamic parameters were IC50 of 14.0 mg/L (9.5%), kout of 1.62 h-1 (13%), FR of 0.56 (8.2%), and Hill coefficients that ranged from 1.26 to 3.34 units. A single 1200 mg dose of etodolac ER given once daily was shown to provide substantial efficacy for 13 hours after dose, modest effect through 24 hours, and a more sustained duration of action than the IR dosage form.

Adolescent↗

PubMed1998

Different protein kinase C isoenzymes regulate IL-2 receptor expression or IL-2 synthesis in human lymphocytes stimulated via the TCR.

Stimulation of purified human PBL with mAbs raised against the T cell receptor resulted in an immediate and transient activation of protein kinase C-alpha (PKC-alpha) and PKC-theta, peaking at 10 min, whereas PKC-beta, -delta, and -epsilon were translocated with a delay of >90 min and remained activated for up to 2 h. To characterize specific functions of distinct PKC isoenzymes, Abs against different PKC isoenzymes were introduced by means of electropermeabilization. Neutralization of PKC-alpha and -theta resulted in the complete inhibition of IL-2R expression, whereas anti-PKC-beta, -delta, and -epsilon Abs inhibited IL-2 synthesis. Extensive control experiments have shown that neither electropermeabilization nor control Ig influenced PKC activity and cellular functions. Our data thus clearly show that specific PKC isoenzymes regulate different cellular functions in stimulated human lymphocytes.

Antibodies↗

PubMed1996

Interleukin-1 induced signalling: biphasic activation of mitogen-activated protein kinase kinase and mitogen-activated protein kinases in HeLa cells. Involvement of phosphoprotein phosphatases.

Results of this study document a biphasic activation of protein kinases of the MAP kinase cascade-MEK and MAP kinases-upon interleukin-1 stimulation in human HeLa cells. The specific activities of both MEK and MAP kinases were increased within 1 min, declined rapidly to control levels and increased again after 15 min of interleukin-1 stimulation. Inhibition by okadaic acid of serine/threonine specific phosphatases resulted in a marked increase in interleukin-1 stimulated MEK and MAP kinase activities. Elevation by interleukin-1 of the specific activities of MEK and MAP kinases correlated with suppression of serine/threonine phosphatases in the late phase of stimulation. The data indicate, that enhanced phosphorylation of cellular proteins by enzymes of the MAP kinase cascade might represent a fine balance between activated protein kinases and repressed phosphoprotein phosphatase 2A in interleukin-1 stimulated HeLa cells.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1995