Preventive service utilisation as a predictor for emergency dental examinations.

OBJECTIVE: To quantify the relationship between receipt of routine dental care and the use of non-trauma related emergency dental services. DESIGN: A multiple logistic regression was run on administrative dental claim and encounter data. The model dependent variable was the use of non-trauma related emergency dental care. Predictors included previous year oral examinations, radiographs, dental cleanings and, as a control, member age. SETTING: Administrative data were obtained from a dental health maintenance organisation located in the state of Texas. SUBJECTS: Claim and encounter data for 2,947 insured members were used, representing experience from 1995 through 1996. OUTCOME MEASURES: The outcome of interest was the use of non-trauma related emergency dental services. RESULTS: Results demonstrated empirically that those who availed themselves of preventive dental services were significantly less likely to use non-trauma related emergency services (P<0.01). The probability of needing non-trauma related dental services in 1996 was 42.7% lower among those who had an examination in 1995 when compared with those who did not. When analysed in a simple logistic regression, dental cleanings in 1995 were also significantly associated with a decreased probability of needing non-trauma related emergency services. However, this relationship did not hold in the controlled model, which was probably due to multicollinearity. CONCLUSIONS: This study provides evidence of the value of periodic preventive dental examinations and services. Those who receive such services are less likely to use non-trauma related emergency dental services.

Derivatives of 5,6-diphenylpyridazin-3-one: synthetic antimitotic agents which interact with plant and mammalian tubulin at a new drug-binding site.

A series of derivatives of 5,6-diphenylpyridazin-3-one (DPP) was examined for interactions with calf brain tubulin following the demonstration that many members of the class caused significant mitotic effects in intact animals, while others had activity against murine P388 leukemia. In L1210 cells several DPP derivatives caused a rise in the mitotic index which correlated well with the cytotoxicity of the drugs. Active DPP derivatives markedly stimulated tubulin-dependent guanosine triphosphate hydrolysis and inhibited tubulin polymerization or induced tubulin oligomer formation, depending on specific reaction conditions. These new agents, however, did not interfere with the binding to tubulin of radiolabeled colchicine, vinblastine, maytansine, or guanosine triphosphate. They thus appear to bind at a previously undescribed site on the tubulin molecule. Some DPP derivatives have significant herbicidal activity, causing mitotic disruption and a rise in the mitotic index in seedling root tissues. Although the DPP derivatives most toxic to plant tissues differ from those most active in inhibiting calf brain tubulin polymerization, virtually all active compounds bear a nitrile substituent at position 4 of the pyridazinone ring. Most active derivatives also bear substituents of varying structure at position 2 of this ring, but no clear structure-function pattern is apparent at this position. The phenyl rings in the most active herbicidal DPP derivatives either are unsubstituted or bear fluorine atoms. Derivatives with chlorine substituents have no detectable herbicidal activity. In contrast, interactions with calf brain tubulin are substantially enhanced if the phenyl rings bear chlorine substituents.

Effect of structural change on acute toxicity and antiinflammatory activity in a series of imidazothiazoles and thiazolobenzimidazoles.

The effect of structural change on the biological activity of a series of imidazothiazoles and thiazolobenzimidazoles is described. It was found that compounds with polar substituents at the 2 or 3 position of the ring system are less acutely toxic while maintaining antiinflammatory activity. Other structural changes, such as the incorporation of a gem-dimethyl substituent in the 6 position, increase acute toxicity and eliminate antiinflammatory activity. The compound with the best activity/toxicity ratio contains an alkyl sulfonyl substituent on the thiazole ring. The thiazolobenzimidazole analogues are more potent than the imidazole analogues.

Isolation and identification of impurities in 4-acetyl-2-(2'-hydroxyethyl)5,6-bis(4-chlorophenyl)-2H-pyridazin-3-one, an antihypertensive agent.

Three trace impurities found in 4-acetyl-2-(2'-hydroxyethyl)-5,6-bis(4-chlorophenyl)-2H-pyridazin-3-one (II), a novel antihypertensive agent, were isolated by a combination of low-pressure liquid chromatography and preparative TLC. These impurities were identified as the formate ester of II, a pyridazinone having a 2-methyl rather than the 2'-hydroxyethyl substituent, and a bis(pyridazinonyl)methane analog. In addition, the product of O-alkylation rather than of N-alkylation of 4-acetyl-5,6-bis(4-chlorophenyl)-2H-pyridazin-3-one (I) with ethylene carbonate was detected by high-performance liquid chromatography. The biological activity of these four impurities was compared to that of II.

Antihypertensive 5,6-diarylpyridazin-3-ones.

The synthesis of a series of 5,6-diarylpyridazinones is described. Some members of this series display an antihypertensive effect in both the spontaneously hypertensive rat (SHR) model and the deoxycorticosteroid (DOCA) model of hypertension. The most potent compounds in the series have halogen substituents on the 5,6-diphenyl rings, a beta-substituted alkyl group at the 2 position of the ring, and acetyl or cyano substituent at the 4 position.

Lipophilic and hydrophilic esters of 4-acetyl-2-(2-hydroxyethyl)-5,6-bis(4-chlorophenyl)-2H-pyridazin-3-one as antihypertensive agents.

In an attempt to enhance the antihypertensive activity of 4-acetyl-2-(2-hydroxyethyl)-5,6-bis(4-chlorophenyl)-2H-pyridazin-3-one, 1, a series of lipophilic and hydrophilic esters was synthesized. These derivatives possessed increased lipid and aqueous solubility, respectively. The esters, in general, cause a larger blood-pressure drop than 1 when tested at high doses in the spontaneously hypertensive rat (SHR) model. At lower doses the antihypertensive activity is the same as with 1.

Inhibition of Streptococcus faecalis by long chain aliphatic monoamines: quantitative structure-activity studies.

Primary, secondary, and tertiary long chain aliphatic amines were synthesized, and their activity against Streptococcus faecalis was determined. Quantitative structure-activity analyses were carried out based on the Hansch extrathermodynamic model, using partition coefficients, CMC's, quantum mechanical charges on the amine nitrogen, and the Taft steric parameter. The best correlations were obtained with the CMC. Steric properties of the ammonium head become important for tertiary amines. The structural feature of these compounds that dominates biological activity is the length of the alkyl tail. Ammonium head substituents are of only secondary importance.

Chemistry and antibacterial activity of nitrobenzofurans.

Thirteen 2-methylbenzofurans were synthesized and their antibacterial activity was investigated. 2-Methyl-3-nitrobenzofuran and analogs containing 7-NO2, 5-NO2, 7-Br, 7-CONH2, and 7-CF3 substituents are bacteriostatic. The spectrum of activity of these compounds is similar to nitrofurazone; however, a strain of E. coli Br which has increased resistance to nitrofurazone did not show increased resistance to 3,7-dinitro-2-methylbenzofuran (1). The 3-nitro-2-methylbenzofurans are labile in solution (T1/2 0.8-3.5 hr at 37 degrees, pH 7.0). The solvolysis product of 1 was identified as alpha,6-dinitro-o-cresol (15). The 3-nitrobenzofurans are more potent in minimal media than in Penassay broth. This greater potency can be abolished by addition of casamino acids and tryptophan to the minimal media.

Structure-activity studies on inhibition of Streptococcus mutans by long-chain aliphatic diamines.

A series of long-chain aliphatic diamines, R1R2N(CH2)mNR3-CnH2n+1' was tested for in vitro inhibition of Streptococcus mutans. In general, high activity was found for all analogs with alkyl chains containing 14 to 18 carbons. The nature of the substituents on the remainder of the alkylenediamine were of secondary importance. N-hydroxyethyl substituents tend to decrease activity. Good correlations of activity with quadratic functions of diamine critical micelle concentrations were obtained.

Quantitative studies of in vitro inhibition of Streptococcus mutans plaque formation by organic amines.

The abilities of five, long-chain aliphatic monamines to inhibit the deposition of plaque formed by Streptococcus mutans on stainless-steel wires were determined. The compounds along with their relative inhibitory potencies that were studied are N-methyltetradecylamine, hexadecylamine, dodecylamine, N-ethyldodecylamine, and octylamine. Activities are compared with critical micelle concentrations, partition coefficients, and quantum mechanical charges on the amine nitrogens.

Synthesis and CMC determination of a series of aliphatic diamines.

Fifteen aliphatic diamines substituted with one long alkyl chain (C10-C18), a varying number of methylene groups separating the nitrogens (two to six), and various aliphatic substituents were synthesized and their CMC's were determined. While the length of the long alkyl chain plays a dominant role in influencing the CMC, the other N-alkyl substituents as well as the length of the methylene chain separating the two nitrogens of the diamine are significant factors.