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Biomedical subjects

W T Harris

Publications and source records attributed to W T Harris.

14 recordsLinked to original sources

Synthesis and evaluation of N-acetylprolinate esters - novel skin penetration enhancers.

A series of N-acetylproline esters (alkyl side chain length, 5-18) were synthesized and tested for potential skin penetration enhancement activity using modified Franz diffusion cells and hairless mouse skin as the penetration barrier. Benazepril and hydrocortisone were used as model drugs and were applied as saturated solutions in propylene glycol. The enhancers were added at a concentration of 5% (w/v). Drug flux, permeability coefficient and enhancement ratios for permeability coefficient were determined. Azone was used as the positive control. While all the compounds tested increased the skin penetration of hydrocortisone, the 5- and 8- carbon esters had no significant effect on the skin penetration of benazepril. The highest fluxes were obtained with 11, 12, and 18-carbon esters and they were comparable to Azone. There was no significant difference between the fluxes obtained with 2 and 5% (w/v) concentrations of the 12-carbon ester on hydrocortisone permeation. The 16-carbon ester, where ethanol was used as a cosolvent, significantly increased the fluxes of both the drugs compared to the control. Differential scanning calorimetric studies suggested that the enhancers may be acting on the lipids of the stratum corneum and their effect was similar to that of Azone. The membrane/vehicle partition coefficient studies indicated an increase in benazepril partition coefficient with enhancer treatment compared to the control. Maximum flux increase was obtained with the 11 and 12 carbon (alkyl chain length) esters for both benazepril and hydrocortisone. The 18- carbon ester which has a cis-double bond in the alkyl side chain, also increased the flux significantly.

Animals↗

n-pentyl N-acetylprolinate. A new skin penetration enhancer.

The activity of n-pentyl N-acetylprolinate (PNAP) as a transdermal penetration enhancer was investigated. PNAP was synthesized from L-proline by acetylation with acetic anhydride, followed by acid-catalyzed esterification with 1-pentanol. Structure confirmation was accomplished by IR and NMR spectroscopy and elemental analysis. Benzoic acid (BA) was used as a model drug, and the effect of PNAP on the flux of BA through human cadaver skin was evaluated. The central nervous system (CNS) toxicity of PNAP was evaluated by comparing the effects of intraperitoneal administration of PNAP to mice with those of laurocapram (Azone), a known penetration enhancer. Based on preliminary studies, PNAP appears to be an effective transdermal penetration enhancer, is nontoxic at low doses, and exhibits dose-related CNS toxicity at higher doses.

Administration, Cutaneous↗

The microscopic appearance and effect of toothbrushing on extrinsically stained metal-ceramic restorations.

To clarify the nature and longevity of the extrinsic stain layer of metal-ceramic restorations, a series of experiments were undertaken. It was found, with microscopic examination, that there is little or no diffusion of the stain into the underlying porcelain and that at a thickness of 22 microns the extrinsic stain layer is grossly evident to an observer. Using a fluoride dentifrice caused no significant loss of either stain or surface integrity with 120,000 brush strokes (equivalent to 8.5 years). At 160,000 strokes (equivalent to 11.4 years) there was evidence of loss of surface integrity.

Color↗

A study of bubbles in a rubber elastomer manipulated under clinical conditions.

One hundred addition reaction silicone impressions were made by students and faculty members using two types of syringes with two syringe tip sizes. A count of the bubbles in the impressions revealed a total of 439 with only one impression completely free of bubbles in either the posterior or anterior test regions. Faculty members, presumably more experienced, confirmed the last out-fewer bubbles hypothesis developed in a previous laboratory investigation, but some students did not. A pneumatically activated syringe produced no fewer bubbles than did the conventional hand-powered syringe but most of the students and faculty members thought it was advantageous. Half believed that more practice with it would be beneficial. We recommend that practicing dentists try to minimize bubbles by extruding the first part of the syringe contents onto the mixing pad or in a distant intraoral location before injecting around the critical tooth preparations.

Air↗

Darmstoff analogues. 2. Ring and side-chain effects on smooth-muscle contraction.

2-cis-delta 8-Heptadecenyl-4-(hydroxymethyl)-1,3-dioxolane monosodium phosphate (1b) has been shown to be present as a major component of Darmstoff in mammalian intestine and to be a potent inducer for contraction of intestinal smooth muscle. The analogous 2-pentadecyl material 1a, also found abundantly in the intestine, is inactive. In this study, synthesis of phosphorylated hydroxymethyl-1,4-dioxanes, -tetrahydrofurans, -cyclopentanes, and -oxathiolanes bearing both oleyl and palmityl side chains is reported. Of these, 2-(hydroxymethyl)-5-cis-delta 8-heptadecenyl-1,4-dioxane monosodium phosphate (2b) exhibits about 12% of the activity of 1b. Its pentadecyl analogue 2a, like 1a, is totally inactive, as are all other compounds prepared. The results indicate that Darmstoff-like compounds exhibit specific chemical requirements for activity and that where activity is encountered, the side-chain specificity noted in 1a and 1b can be preserved.

Animals↗

Provisional restorations for traumatically injured teeth requiring endodontic treatment.

The acid-etch-composite resin technique is used to retain a provisional restoration during the course of endodontic treatment. As described, the use of a gutta percha cone during the buildup and bonding to adjacent teeth provides the following: (1) good esthetics during endodontic treatment, (2) good support for rubber dam placement, (3) good entry to the canal, (4) good coronal seal for medication within the canal, and (5) good function as required by the provisional crown.

Acid Etching, Dental↗

Conditioning dentures for problem patients.

We have had considerable success with difficult patients through the use of conditioning dentures. Patients with severe gagging problems have been able to gradually accustom themselves to the presence of dentures in the privacy of their homes and at their own rate of progression. Patients without previous denture experience are given a chance to adjust to problems of speech, salivation, and taste prior to receiving their new dentures. We believe that conditioning dentures should be a part of the treatment sequence for all patients being prepared for their first dentures. Many problems are faced by the new denture patient, and anything the dentist can do to prepare him for this difficult time can increase the chances for success.

Adaptation, Physiological↗