DIMETHYLSUBERIMIDATE AS A PULPOTOMY AGENT

THE LONG-TERM GOAL OF THIS APPLICATION IS TO DEVELOP DIMETHYLSUBERIMIDATE (DMS) AS AN ALTERNATIVE PULP THERAPY. FORMOCRESOL, THE DRUG MOST COMMONLY USED FOR TREATMENT OF CARIOUSLY EXPOSED PULPS OF THE PRIMARY DENTITION, IS TOXIC TO THE TREATED TISSUE, INDUCES ANTIGEN FORMATION AND SUBSEQUENT CHRONIC INFLAMMATION, IS RAPIDLY DISTRIBUTED SYSTEMICALLY, AND HAS MUTAGENIC POTENTIAL. FORMOCRESOL PULPOTOMIZED TEETH ARE OFTEN EXFOLIATED PREMATURELY WITH DETRIMENTAL EFFECTS TO THE DEVELOPING SECONDARY DENTITION. GLUTARALDEHYDE IS USED CLINICALLY AS AN ALTERNATIVE TO FORMOCRESOL, BUT MANY OF THE SAME DANGERS EXIST. DMS IS A DIIMIDOESTER USED AS A CROSS-LINKING AGENT IN BIOCHEMISTRY AND AS AN ELECTRON MICROSCOPIC FIXATIVE. REAGENT WHICH DOES NOT INTERACT WITH PROTEIN HYDROLYZES SPONTANEOUSLY TO A NONREACTIVE MOLECULE. UNLIKE FORMOCRESOL AND GLUTARALDEHYDE, DMS DOES NOT INDUCE AUTOANTIGEN FORMATION SINCE THERE IS NO NET CHANGE IN CHARGE OF THE PROTEIN AFTER CROSS-LINKING. THIS SUGGESTS THAT DMS IS A REASONABLE ALTERNATIVE FOR PULP THERAPY, POTENTIALLY REPLACING FORMOCRESOL OR GLUTARALDEHYDE FOR TEETH PREDESTINED TO EXFOLIATE AND AS A CONSERVATIVE TREATMENT FOR ENDODONTIC INFLAMMATION IN ADULT TEETH. PHASE I RESEARCH WILL DETERMINE THE TOXICITY OF DMS FOR CULTURED ODONTOBLASTS BY EXAMINING CELL VIABILITY AFTER INCUBATION WITH DMS AT VARYING CONCENTRATIONS AND FOR VARYING TIME PERIODS. CELL DAMAGE WILL BE QUANTITATED BY MEASURING ENZYME ACTIVITY IN THE CULTURE MEDIUM. CELL RECOVERY AFTER TREATMENT AND ABILITY OF DMS TO CROSS-LINK PROTEINS WILL BE ASSESSED BY ONE- AND TWO-DIMENSIONAL SDS-PAGE OF CELL PROTEINS, PROTEINS RELEASED INTO THE CULTURE MEDIUM, AND TOTAL PULP PROTEIN BEFORE AND AFTER TREATMENT. THESE DATA WILL BE USED TO ESTABLISH DOSAGES FOR CLINICAL TRIALS IN PHASE II.