Comparison of unbound and total serum theophylline concentrations with those of stimulated and unstimulated saliva in asthmatic children.

Unstimulated saliva, citric acid stimulated saliva, and serum were collected from 31 asthmatic children taking theophylline. Salivary theophylline concentrations, and total and unbound serum theophylline concentrations were measured. The correlation coefficients between both types of saliva, and total and unbound serum theophylline were all statistically significant (p less than 0.001). The highest correlation coefficients were obtained with stimulated saliva and total serum concentrations (r = 0.98), and stimulated saliva and unbound serum (r = 0.96). The coefficients when unstimulated saliva was compared to either total or unbound serum concentrations were 0.90 and 0.89, respectively. Serum binding of theophylline averaged 58.1%. Unstimulated saliva had a higher mean theophylline concentration than stimulated saliva. The results suggest that salivary monitoring using stimulated saliva may be used to predict serum concentrations with a high degree of confidence when the saliva levels are substantially lower than, higher than, or in the middle of the therapeutic range, but there is a considerable degree of uncertainty when the salivary values are near the lower or upper end of the therapeutic range.

Effects of 5-fluorouracil on protein synthesis and secretion of the rat parotid gland.

100 mg/kg of FU were injected intraperitoneally once daily for three days. Animals were anaesthetized with 50 mg/kg of sodium pentobarbital before cannulation of the parotid duct. The total volume, amylase and protein content of the saliva were determined after stimulation with either 5 mg/kg pilocarpine or 5 mg/kg isoproterenol in FU-treated, pair-fed, and control animals. Saliva from FU-treated animals was significantly lower (p less than 0.05) in volume, amylase and protein content than that of both control groups. SDS, anionic and cationic gel electrophoresis of parotid saliva revealed no qualitative changes in the types of proteins secreted. FU reduced the total glandular amylase per unit DNA in both unstimulated and isoproterenol-stimulated parotids (p less than 0.05). Decreased protein synthesis may be the mechanism underlying the depleted secretory protein stores because the contents of isolated secretory granules from experimental glands contained less radiolabelled protein than those of either control group, and whole-gland homogenates had marked reductions in the activities of three lysosomal enzymes and in total RNA content. The secretory granules of experimental animals contained less labelled protein than those of controls, but experimental animals secreted a greater proportion of their total glandular radiolabelled secretory protein into saliva relative to amylase, suggesting that newly synthesized secretory proteins were preferentially secreted.

Effect of methotrexate on protein and amylase secretion by rat parotid and submandibular salivary glands.

Saliva was collected from anaesthetized, methotrexate (MTX)-treated, pair-fed and control rats using either acetylcholine or bethanechol as secretagogue. Parotid saliva was analysed for protein and amylase content, and submandibular saliva for protein. Acetylcholine stimulation after MTX increased parotid protein output by 151 per cent, amylase output by 125 per cent and submandibular protein output by 229 per cent when compared to control values. There were no significant differences in either protein or amylase output between the control and pair-fed animals. With bethanechol, salivary amylase and protein secretion did not differ between MTX-treated and control animals. The significant increase in parotid protein and amylase output with acetylcholine was reduced by pretreatment with hexamethonium (5 mg/kg) or propranolol (5 mg/kg), but not by phenoxybenzamine (1 mg/kg). MTX did not increase the number or the dissociation constant of parotid beta-adrenergic receptors but did increase their number in the submandibular gland. Thus increases in protein and amylase output caused by acetylcholine MTX-treated rats may be the result of increased beta-adrenergic activity.

The influence of plasma catecholamines on methotrexate-enhanced rat salivary gland protein secretion.

The acetylcholine-elicited secretory output of parotid protein and amylase, and of submandibular protein from rats receiving 15 mg methotrexate (MTX)/kg for 3 days were 3-6 times greater than that from control animals. Plasma epinephrine and norepinephrine levels in MTX-treated animals were 4-14 times greater than control values. Adrenalectomy reduced the plasma-catecholamine levels, and the acetylcholine-stimulated salivary protein and amylase output. Thus MTX-enhanced salivary protein secretion evoked by acetylcholine stimulation may be mediated, at least in part, by elevated levels of circulating catecholamines.

Methotrexate-induced changes in rat parotid and submandibular gland function.

Methotrexate (MTX) was injected intraperitoneally at a dose of 15 mg/kg into adult rats daily for three consecutive days. When compared with saline-injected, ad libitum-fed rats or pair-fed saline-injected rats, MTX decreased unstimulated parotid gland weight, RNA content, and amylase content. RNA content was also decreased in submandibular glands. The parotid and submandibular gland outputs of sodium and chloride, but not that of potassium, were decreased following MTX injection. Ductal perfusion demonstrated decreased net efflux of sodium and chloride from the excretory duct of the submandibular gland. The effects of MTX on unstimulated parotid gland weight, RNA content, and amylase content are consistent with its ability to inhibit protein synthesis through depletion of folate co-factors. However, the mechanism by which the alterations in ion transport occurred is not clear at this time.

Surfactant-induced alterations of permeability of rabbit oral mucosa in vitro.

The permeability of rabbit oral mucosa to eight nonelectrolytes was measured in vitro in the absence and in the presence of 0.025, 0.1, and 1.0% concentrations of anionic, cationic, and nonionic surfactants. The anionic surfactant sodium lauryl sulfate and the cationic surfactants cetyltrimethylammonium bromide and cetylpyridinium chloride caused greater increases in permeability than polysorbate 80, a nonionic surfactant. The increases in permeability brought about by the surfactants were concentration dependent.

Effects of surfactants on the permeability of canine oral mucosa in vitro.

The effect of 3 cationic, 1 anionic, and 1 non-ionic surfactant on the permeability of oral frenulum removed from anesthetized dogs was determined in vitro. Permeability to 12 organic compounds was measured in the presence and absence of surfactant. Cetylpyridinium chloride, cetyltrimethylammonium bromide, benzalkonium chloride and sodium lauryl sulfate, at concentrations from 0.025-1.0% caused dose-related increases in permeability to each of the solutes tested, whereas polysorbate 80 caused an increase in permeability to only 3 solutes, and this occurred only at the highest surfactant concentration employed.

Surfactant-induced increases of permeability of rat oral mucosa to non-electrolytes in vivo.

The effect of non-ionic, cationic and anionic surfactants on non-electrolyte permeability of rat oral mucosa in vivo was tested. The surfactants caused an increase in mucosal permeability to oil-soluble compounds and small and large water-soluble compounds. The effect was concentration-dependent, and both the cationic and anionic surfactants were more potent than the non-ionic compounds. Surfactant-treated tissue showed widening of the stratum corneum due to separation of layers and loss of surface layers. Measurement of the permeability to sodium lauryl sulphate indicated that this anionic surfactant produced damage to the permeability barrier.

Permeability of the rat oral mucosa to organic solutes measured in vivo.

The permeability of the oral mucosa to organic solutes of different molecular volumes, oil-to-water distribution coefficients, and pKa was studied in an in-vivo system. The calculated permeability coefficients were independent of time of application and the concentration of the solutes, a finding consistent with transport by simple diffusion. The permeability of organic acids was pH dependent whereas permeability to compounds with a degree of ionization that did not change over the pH range was not affected by pH. Increasing the chain length from two to eight carbons in an organic acid series resulted in an increase of both the oil-to-water distribution coefficient and the permeability coefficient; the permeability coefficient was decreased by the addition of oxygen in the form of hydroxyl groups. These results indicate that there is similarity in the way that lipid-soluble substances diffuse across oral mucosa and other lipid membranes. Results using compounds with oil-to-water distribution coefficients less than that of water suggest that these compounds traverse the oral mucosa by two additional routes. One, for compounds with molar volumes less than 80 cm3/ml, is via pores; whereas, the second, utilized by larger compounds, is probably by an intercellular route.

Pharmacology of antibiotics used in dentistry.

The term antibiotic is now generally used to include antimicrobial substances produced by chemical means as well as those produced by micro-organisms. They may be either bacteriostatic or bacteriocidal. A bacteriostatic antibiotic inhibits the growth and replication of bacteria thereby giving the body's natural defence mechanisms time to become effective in overcoming an infection. In the majority of cases, and particularly in patients whose natural resistance is lowered by disorders of the immune system, it is preferable to choose a bacteriocidal agent. The first bacteriocidal antibiotic was penicillin G. The structure of the penicillin molecule is discussed as a basis for the understanding of its mode of action and of the mechanisms which lead to bacterial resistance. The modified and semisynthetic derivatives of penicillin are discussed and specific indications for their use are described in detail. Alternatives to the use of penicillin are also discussed and particular attention is paid to the cephalosporins and the tetracyclines.

Effect of chemical structure on nonelectrolyte penetration of oral mucosa.

The in vitro permeability of oral mucosa from New Zealand rabbits to 17 nonelectrolytes was studied using radioactive tracer techniques. Calculated permeability coefficients were independent of solute concentration and were similar when measured from outer to inner surface or inner to outer surface. Generally, an increase in chain length and increased lipid solubility within a series of alcohols or diols resulted in increased permeability. However, the first member of each series displayed anomalous behavior in that it penetrated more rapidly than the second member of the series. Addition of one or more hydroxyl groups to a compound brings about a decrease in permeability. The addition of a second or third hydroxyl group has less of an effect in decreasing permeability if it is adjacent to an existing hydroxyl as compared to when it is further separated. Addition of a hydroxyl group to a compound decreases permeability to a greater extent than addition of a ketone. Also, replacement of a hydroxyl group with an amide results in decreased permeability. These results point out the importance of lipid solubility and ability to form hydrogen bonds to permeability.

Calcium mediation of cholinergic-stimulated amylase release from mouse parotid gland.

Amylase release from mouse parotid fragments was stimulated independently by cholinergic and beta-adrenergic agents. The cholinergic agonist, carbachol, significantly increased release of amylase only in Ca2+ containing medium whereas isoproterenol-stimulated amylase release was unaffected by Ca2+ removal. The ionophore, A23187, mimicked the effect of cholinergic stimulation when Ca2+ was present in the medium. Uptake of 45Ca2+ into tissue fragments was enhanced by carbachol and A23187 but not by isoproterenol; atropine blocked the effect of carbachol. Diphenylhydantoin (DPH) and verapamil partially inhibited carbachol-stimulated amylase release and 45Ca2+ uptake, whereas diazoxide potentiated these effects; in all cases there was good parallelism between 45Ca2+ uptake and amylase release. It was concluded that the primary step in the release of amylase from mouse parotid gland in response to cholinergic agents is an increased influx of Ca2+.

HCO-3-ATPase activity distribution in rat liver cell fractions prepared by zonal centrifugation.

Plasma membrane sheets prepared by zonal centrifugation of a premicrosomal pellet obtained from a rat liver homogenate are devoid of HCO-3-ATPase activity. Since the microsomal fraction is also lacking in this ATPase activity, it can be concluded that the HCO-3-ATPase is not involved in the secretion of HCO-3 into bile.

Physical properties of zinc phosphate cement prepared on a frozen slab.

The physical properties of a zinc phosphate cement prepared on a room temperature slab were compared to those of the cement prepared on a frozen slab. Solubility, compressive strength, and setting time of cements prepared on both types of slabs were within the limits set by A.D.A. Specification No. 8.