In vitro and in vivo effects of indomethacin on phytohemagglutinin-stimulated lymphocyte mitogenesis.

The in vitro and in vivo effects of indomethacin on blastogenesis of rat splenic lymphocytes in response to phytohemagglutinin (PHA) were investigated. Direct addition of indomethacin to lymphocyte cultures was found to have both a stimulatory effect at low concentrations (less than or equal to 0.003 microM) and an inhibitory effect at higher concentrations (greater than or equal to 0.01 microM). The in vitro stimulation was significant only at submaximal and supramaximal concentrations of PHA, whereas the inhibitory response was observed with a wide range of mitogen concentrations. When indomethacin was administered to animals twice daily for 3 days, similar dose-dependent stimulatory and inhibitory effects were observed. Again the stimulatory effects were associated with lower doses (0.1 microgram/kg) and were found to be significant only with submaximal PHA concentrations. The inhibition with higher doses of indomethacin (IC50 = 0.20 mg/kg) was accompanied by a dose-dependent decrease in the maximal response and an increase in the EC50 to PHA in indomethacin-treated animals. These inhibitory effects of indomethacin administration on lymphocyte proliferation were found to occur at doses which closely approximate those required for the anti-inflammatory effects of the drug.

Changes in T and B lymphocyte proliferative responses in adjuvant-arthritic rats: antagonism by indomethacin.

The effects of a potent non-steroidal antiinflammatory drug, indomethacin, on the inflammatory response and lymphocyte proliferation were investigated in adjuvant-arthritic rats. As shown by others, adjuvant produced a time-dependent swelling of the contralateral paw which was maximal within 14 days after administration. Upon the intraperitoneal injection of either 1 or 2 mg/kg of indomethacin, twice daily for 3 days, the swelling of the contralateral paw was completely reduced. Selective changes in proliferative responses of splenic T and B lymphocytes to mitogens were found to accompany these effects. Adjuvant arthritic rats were found to have increased T cell proliferation when stimulated with phytohemagglutinin, whereas proliferation of B lymphocytes in the presence of lipopolysaccharide was completely suppressed. Indomethacin treatment at either the 1 or 2 mg/kg dose was found to depress the proliferative responses of T cells by 60 and 95%, respectively. In contrast, the hyporesponsiveness of B lymphocytes in arthritic animals was partially reversed with 2 mg/kg indomethacin. These results suggest that indomethacin may be exerting an antiinflammatory effect through a selective alteration of T and B lymphocyte activities in lymphoid tissue.

Epulis granulomatosa: extraction sequellae.

Epulis granulomatosa is a post-surgical lesion emanating from an extraction socket. It can be misdiagnosed with lesions of similar appearance, for example, foreign body or pyogenic granulomas, or as a herniation of the maxillary sinus. Based on clinical appearance and microscopic description, granulomas all appear to represent essentially the same lesion. However, pathonomonically, the epulis granulomatosa emanates only from an extraction socket; the other granulomas can be found anywhere in the body.

Confirmed allergic reactions to amide local anesthetics.

Allergic reactions to ester local anesthetics are not uncommon. It is generally accepted that similar reactions to the newer amides do not occur. This assumption should be reconsidered. A confirmed case of true amide allergy is reported.

Inhibition of amino acid transport by nonsteroidal anti-inflammatory drugs: a model for predicting relative therapeutic potency.

Indomethacin has been shown to inhibit selectively the rate of alpha-(methylamino)-isobutyric acid (MeAIB) uptake by the "A" transport system in several cell types. This study was undertaken to determine if this activity was shared by other nonsteroidal anti-inflammatory drugs (NSAID), if the inhibition of MeAIB transport was unique to drugs with anti-inflammatory activity and finally if it could be correlated with their in vivo potency in humans and in animal test systems. Utilizing BRLT rat hepatocyte cultures (hepatocytes cloned from Buffalo rats); it was found that all of the acidic NSAID tested inhibited MeAIB uptake in a dose-dependent manner with IC50 values in the low to midmicromolar range. The amount of inhibition was dependent on cell density, time of incubation with drug, the media pH and its concentration of protein and amino acids. The order of potency of the acidic NSAID in inhibiting MeAIB uptake was found to be correlated closely with their potency in the inhibition of prostaglandin synthesis in vitro, the suppression of induced inflammatory reactions in rats and the maximum recommended daily doses in humans. Pharmacologically inactive metabolites of several NSAID had little or no effect on MeAIB transport at concentrations up to 10 times greater than active parent compounds. Other compounds tested, including glucocorticoids, were found to have little effect on the rate of MeAIB uptake. These studies indicate that the inhibition of MeAIB uptake in BRLT cells may represent a reliable and rapid screen for predicting the therapeutic potency of newly developed NSAID.

Stability of local anesthetics in the dental cartridge.

Recent manufacturer recalls of local anesthetics have emphasized the problems with storage stability. This article reviews the principles of drug stability, mechanisms of degradation of commonly used vasoconstrictors, research on the stability of commercially produced local anesthetic preparations, and possible effects of the container-closure system. The review concludes with a list of practical and clinical suggestions on how to minimize storage stability problems with dental local anesthetics.

Single-dose vicoprofen compared with acetaminophen with codeine and placebo in patients with acute postoperative pain after third molar extractions.

PURPOSE: The purpose of this double-blind, randomized study was to compare the efficacy and safety of a single dose of the following medications: 2 tablets of Vicoprofen (ibuprofen 200 mg/hydrocodone 7.5 mg; Knoll Pharmaceutical Co, Mount Olive, NJ), 2 tablets ofp6 acetaminophen with codeine phosphate (acetaminophen 300 mg/codeine 30 mg), and 2 tablets of placebo in the management of moderate to severe postoperative dental pain after surgical extraction of at least one impacted mandibular third molar. PATIENTS AND METHODS: One hundred twenty-five patients (75 women, 50 men) participated in the study. The time of first perceptible pain relief and meaningful pain relief were measured using a stopwatch technique. Pain intensity and pain relief scores were recorded using standard verbal descriptors at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, and 8 hours after dosing. At the conclusion of the study, patients completed a global evaluation for the effectiveness of the study medication. RESULTS: Both active treatments were superior to placebo for all analgesic measures. Pain relief scores were significantly better for Vicoprofen than placebo throughout the study and significantly better than for acetaminophen with codeine from 2 through 8 hours after dosing. The duration of analgesia (time to remedication) was significantly longer for Vicoprofen (median, 5.50 hours) compared with acetaminophen with codeine (median, 3.03 hours) and placebo (median, 1.00 hours). Mean global evaluation for Vicoprofen was significantly better than for placebo and acetaminophen with codeine. Overall, there were no significant differences in the adverse event profile among the 3 treatment groups. CONCLUSIONS: Vicoprofen was found to be an effective postoperative analgesic medication in the management of acute postoperative dental pain. Its total analgesic effect, duration of analgesia, and global evaluation were superior to acetaminophen with codeine and placebo in this study model.