Effect of smear layer removal on the diffusion permeability of human roots.

Ten human maxillary incisors, extracted because of periodontal disease or nonrestorable caries, were obtained and instrumented to a size #70 K-Flex file at the working length using a standard stepback technique. Tritiated water (3H2O) was placed in the root canals and allowed to diffuse to the external surface of the roots until it reached a constant rate. The smear layer in each of the experimental roots was then removed using 0.5 M EDTA followed by 5.25% sodium hypochlorite (NaOCI). The constant rate diffusion of 3H2O was remeasured. The roots were then stored in deionized H2O for 2 months and the constant rate diffusion of 3H2O was remeasured. A statistically significant difference was noted between all three groups. A decrease in the diffusion permeability of the root to 3H2O was noted immediately after smear layer removal and the highest permeability was recorded after storage in the deionized water for 2 months.

Permeability of root dentin to epinephrine released from gingival retraction cord.

The permeation of racemic epinephrine across roots of human molar crown segments was studied in vitro. Permeation was measured in the presence of cementum, with cementum removed (dentin exposed), and with and without dentin smear layers. Epinephrine was initially detected at 10 minutes and reached a steady state in 70 minutes. Epinephrine flux (the product of concentration and the flow rate per unit of dentin surface area) significantly increased when both the cementum and dentin smear layers were removed. The T1/2 (half-time in minutes necessary to reach steady-state diffusion) was zero with intact cementum and increased to approximately 40 minutes in dentin with and without smear layers. This study suggests that the permeation of epinephrine across root surfaces is prevented by the presence of cementum and retarded by the presence of dentin smear layers. Also, the data suggest that root dentin is another source of absorption when epinephrine-impregnated retraction cord is applied to the gingival sulcus.

Medication of the dental pulp: a review and proposals.

For years, dentists have desired to treat the intact dental pulp. Since it is well-known that many substances, including some drugs, are capable of permeating dentin, we believe it is possible to treat certain types of pulpitis by applying drugs at the base of cavity preparations. Useful drugs include local anesthetics to block pain transmission, glucocorticoids or non-steroidal anti-inflammatory agents (NSAIA) to treat inflammation, NSAIA or narcotic analgesics for pain control, and antibiotics to treat infection. The literature is reviewed and proposals are presented to study medication of the dental pulp.

Pharmacologic management of temporomandibular joint disorders and chronic head and neck pain.

One goal of pharmacology is to break a cycle of pain and spasms. In this cycle, pain leads to muscle spasms, and spasms lead to pain with no physiologic feedback control occurring. A second goal is to break another interacting cycle of pain and inflammation. In this cycle, pain mediators can lead to inflammation and the inflammation itself can contribute to pain. The two cycles perpetuate each other because they have many interacting factors in common. Drugs are useful either alone or to supplement other forms of therapy that can break the pain/spasm cycle, as well as the pain/inflammation cycle. This article discusses the many types of drugs available to the clinician today. Although the original version of this article was published by the first author in 1973, the number of new drugs (including some new classes of agents) and newer concepts of pain that have been introduced have required further updating.

Epinephrine permeation across dentin in vitro.

The permeation of epinephrine across human dentin discs was studied in vitro. Permeation was measured across dentin of two different thicknesses, with and without the presence of smear layers. Epinephrine was readily detected at the earliest measured time (10 min) and reached peak concentrations between 30 and 50 min. Epinephrine flux (concentration multiplied by the volume of the effluent per min) increased with decreasing thickness of the discs and increased significantly with the removal of the smear layer. The T 1/2 (half-time in min necessary to reach steady-state diffusion of epinephrine) decreased as dentin thickness was reduced and fell further in the absence of the smear layer. This study suggests that the permeation of epinephrine across dentin is inversely related to dentin thickness and retarded by the presence of a smear layer. Also, the topical use of 1 mg/ml epinephrine produced therapeutically useful drug concentrations, but the rate of permeation was relatively slow.

Perdeuteration of methoxyflurane reduces production of fluorometabolites in mice.

The fluorometabolites of perdeuterated methoxyflurane (D-MOF) compared to the nondeuterated form (H-MOF) were studied in mice. Inorganic fluoride (F) and an organic acid labile fluorometabolite (OALF) were determined at various post-administration times. At 100 minutes after D-MOF, F was decreased 32-38% and OALF was down to 33-45%. After 300 minutes F was 56% less and OALF was 46% less after D-MOF administration. OALF increased 35-38% when H-MOF and D-MOF were diluted in oil compared to the undiluted forms. At three times (10, 30, and 100 minutes) D-MOF resulted in reductions of F to 31-38% of values produced by H-MOF. Also, OALF was reduced to 38-46% with D-MOF compared to H-MOF. These studies suggest that the use of D-MOF in mice results in a significant decrease in the appearance of the fluorometabolites F and OALF. The accumulation of metabolites is thought to be responsible for nephrotoxicity of MOF; therefore, D-MOF should be a much safer agent for use in general anesthesia.

Use of verbal descriptors, thermal scores and electrical pulp testing as predictors of tooth pain before and after application of benzocaine gels into cavities of teeth with pulpitis.

A double-blind pilot study was conducted on 27 consenting human volunteers who had irreversible pulpitis associated with persistent toothache pain from open carious lesions. Formulations tested contained either 0, 10%, or 20% benzocaine and were identified only by a numbered code. Before the experiment started, a small amount of a known 5% benzocaine gel was placed for 1 minute on the tongue of each patient to assure a sensation of numbness within the oral cavity. Then the test tooth was washed with a gentle stream of warm water and dried with gauze. A randomly selected test medication was placed into the open cavity and around the gingival margins for 5 minutes. Pre- and posttreatment tests were conducted at the following timed intervals: 0, 5, 15, 30, 45, 60, 75 and 90 minutes. The tests included degree of pain (rated: 0 = none, 1 = mild, 2 = moderate, 3 = severe); electrical pulp testing (EPT) by a modified, voltage-ramping instrument; and ice water testing (0.5 mL directed quickly onto sound enamel of the tooth and rated: 0 to 4, with 4 being intolerable). After testing, or when pain returned to baseline, endodontic procedures were performed. There was a significant increase (p < 0.032, Fisher exact test) in subjects obtaining pain relief, rated by verbal descriptors, from the benzocaine gels (14 out of 18 improved) compared to placebo (3 out of 9 improved). It was concluded that: 1) benzocaine gels are effective formulations for temporary relief of toothache pain, 2) there were no statistical differences in EPT scores between teeth having pulpitis and control teeth, 3) there were no correlations between direction of EPT scores and pain relief, 4) cold water testing was a good predictor of whether or not a tooth had pulpitis, and 5) changes in cold water testing scores after treatment could not be correlated to relief of pain according to verbal descriptors. The effectiveness of benzocaine in relieving toothache pain verifies previous studies; however, a difference between 10% and 20% benzocaine could not be demonstrated probably because of two factors: 1) the present experiment had a small sample size, and 2) there was no direct measurement of duration of local anesthesia.

Further characterization of tetracycline's quantitative binding to dentin.

Unerupted human third molar crown segments were used to measure the change in the concentration of 3H-tetracycline that occurs when it moves across dentin from pulpal to occlusal surfaces. When 1.25, 2.5, and 5 x 10(-5) M 3H-tetracycline were filtered across dentin, binding increased by 21, 51, and 69%, respectively. When the same concentrations of 3H-tetracycline were preloaded onto crown segments and eluted with 1.1 x 10(-3) M nonradioactive tetracycline, the percentage of elution of 3H-tetracycline was not significantly different over time. When preloaded 3H-tetracycline was displaced by diffusion with water or 1.1 x 10(-3) M nonradioactive tetracycline, there were no significant differences. There was a significant difference between the rate of displacement of 1.25 x 10(-5) M 3H-tetracycline and the other two preloaded concentrations when 5.8 x 10(-4) M 3H-tetracycline/tetracycline was used as the eluant. These data suggest that the binding of 3H-tetracycline to dentin was concentration dependent and that 3H-tetracycline binds nonspecifically and reversibly.

The effect of cimetidine on the formation of methoxyflurane fluorometabolites in mice.

Pre-dosing of mice with cimetidine reduced the plasma levels of inorganic fluoride, one of the fluorometabolites of methoxyflurane. The reduction occurred as early as 10 and as late as 160 minutes after cimetidine injection, and it was seen at both 30 and 100 minutes after subsequent methoxyflurane administration. Multiple pre-dosings with cimetidine did not notably affect the fluoride response. These results may be of use in avoiding methoxyflurane toxicity, which is thought to be due to markedly elevated fluoride levels in some patients.

Lidocaine and procaine alter rat brain amines.

Lidocaine HCl (100 mg/kg i.p.) or procaine HCl (240 mg/kg i.p.) was injected into rats, which were killed after zero to 12 min. Six brain parts were analyzed for serotonin, norepinephrine, and dopamine. Lidocaine induced depletion of serotonin and of dopamine in some regions and elevation in others; however, it produced elevated levels of norepinephrine. Not all brain regions showed a significant change of amines. Procaine induced elevations of serotonin, norepinephrine, and dopamine; norepinephrine elevation occurred in a few brain parts, whereas serotonin and dopamine levels were elevated in all brain regions.

Alteration of lidocaine- or procaine-induced convulsions by manipulation of brain amines.

Lidocaine and procaine seizure thresholds were studied. The i.p. median convulsant dose (CD50) of lidocaine and procaine with saline pre-treatment was 95 and 240 mg/kg, respectively. Dopamine depletion by pre-treatment with d1-alpha-methyl-p-tyrosine plus dihydroxyphenylserine resulted in a significant drop of CD50 to 69 and 175 mg/kg for lidocaine and procaine, respectively. Serotonin depletion by pre-treatment with p-chlorophenylalanine resulted in a significant drop of CD50 to 68 mg/kg for lidocaine, but no significant change for procaine.

Anticaries and antiplaque potential of free-fatty acids in vitro and in vivo.

The efficacy of several fatty acids as antimicrobial, antiplaque, and anticaries agents, as well as their ability to inhibit hydroxyapatite dissolution were examined. All effectively inhibited bacterial growth. Lauric, linoleic, and oleic acids decreased plaque formation and lauric acid inhibited hydroxyapatite dissolution. When used in the food, lauric acid decreased caries in rats, but not significantly.

Early appearance of methoxyflurane fluorometabolites in mice.

The biotransformation of methoxyflurane produces two fluorometabolites: inorganic fluoride (F) and an acid-labile fluorocompound (OALF). These have been assayed in the serum of male mice 10, 30, and 100 minutes after either ip or sc injections of 0.7 microliter of methoxyflurane (MOF) per gram of body weight, as either the volatile liquid itself or as a 1:10 dilution in corn oil. During the 10- to 100-minute intervals, the mice were observed for loss of the righting reflex. Corn oil dilution significantly altered the production of MOF fluorometabolites, usually decreasing them, but after 100 minutes, the serum concentration of OALF was 25% greater. Loss of righting reflex was also altered; 11 of 18 mice given undiluted MOF experienced it, whereas only 2 of 18 given the diluted agent did. Compared to the tip route, the sc route resulted in less fluoride at all three time intervals, but more of the OALF after 30 and 100 minutes. None of the sc-dosed mice lost his righting reflex.