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Biomedical subjects

T M Parkinson

Publications and source records attributed to T M Parkinson.

At least 19 recordsLinked to original sources

A polymeric drug for treatment of inflammatory bowel disease.

Sulfasalazine (SASP) consists of salicylic acid azo linked at the 5-position to a pyridine-containing sulfonamide. This drug, currently used in inflammatory bowel disease treatment, is reductively cleaved by anaerobic bacteria in the lower bowel to 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP). Recent reports indicate that 5-ASA is the active therapeutic moiety and that SP is responsible for a variety of adverse clinical side effects. Water-soluble polymer 7, which contains salicylate residues azo linked at the 5-position to an inert polymer backbone, has been synthesized for the site-specific reductive release of 5-ASA in the lower bowel. Preparations of 7 deliver (chemical reduction) greater than 1.96 mmol of 5-ASA/g of polymer. In vitro studies with the polymer in anaerobic rat cecal bacteria demonstrated a reduction rate of approximately 1 mu equiv of azo bond h-1 (mL of cecal content)-1. A pharmacokinetic comparison of polymer and SASP showed similar deliveries of 5-ASA and metabolites to the lower bowel, blood, and urine of orally dosed rats. Polymer 7 proved more active than SASP or 5-ASA in the guinea pig ulcerative colitis model. Potential therapeutic advantages of 7 include nonabsorption/nonmetabolism in the small intestine, direct 5-ASA release at the disease site, and nonabsorption/nonmetabolism of the reduction-released carrier polymer.

Aminosalicylic Acid↗

Metabolic fate of food colorants.

Evaluation of the chemical and biological data on synthetic and natural food colorants indicates that synthetic colorants in general have been studied more thoroughly than their natural counterparts. The increasing use of natural colorants in processed foods at levels higher than those found in natural sources has raised concern about deficiencies in knowledge, in some cases, of their exact chemical composition, stability, metabolic fate, and toxic potential. Additional studies, particularly of comparative metabolic fate in experimental animals and in man and of genotoxic potential, are required. Until studies with natural colorants comparable to those carried out with synthetic colorants have been completed and evaluated, greater safety of natural colorants cannot be assumed.

Animals↗

Intestinal absorption of polymeric derivatives of the food dyes sunset yellow and tartrazine in rats.

1. Absorption and metabolism of 14C-labelled sunset yellow (FD & C Yellow No. 6), tartrazine (FD & C Yellow No. 5) and high molecular weight polymeric derivatives of the two azo dyes were compared in rats. 2. A trace to 1.5 percent of unchanged monomeric dyes was excreted in urine and bile during the first 24 h after dosing. No unchanged dye was absorbed after administration of the polymeric derivatives. 3. In animals dosed with sunset yellow and its polymer derivative, absorption of the azo-bound cleavage product 1-amino-2-naphthol-6-sulphonic acid was 8.5 and 6.9 percent, respectively, while absorption of the cleavage product sulphanilic acid was 37.4 and 0 percent, respectively. 4. In animals dosed with tartrazine and its polymer derivative, absorption of the cleavage product aminopyrazolone and its metabolites was 4.0 and 4.6 percent, respectively. 5. Azo bond cleavage did not appear to be decreased in the polymer derivatives. However, the sulphanilic acid moiety of both dyes remained attached to the polymer backbone, resulting in a 95 percent decrease in sulphanilic acid absorption with polymeric tartrazine. 6. Decreased absorption of unchanged dyes and certain metabolites with the stable, non-absorbed polymeric derivatives may be significant in developing non-sensitizing substitutes for these two commonly used food colourants.

Animals↗

Hypolipidemic effects of orally administered dextran and cellulose anion exchangers in cockerels and dogs.

Various cellulose and dextran anion exchangers bind bile salts in vitro under conditions of pH and ionic strength resembling those in the lumen of the small intestine. Of these substances, diethylaminoethyl (DEAE) cellulose, guanidoethyl cellulose, and DEAE Sephadex reduced hypercholesterolemia when added to the diet of cholesterol-fed cockerels. In addition, DEAE Sephadex reduced serum sterols in normocholesterolemic cockerels and dogs, lowered serum phospholipids and triglycerides in cholesterol-fed hypercholesterolemic cockerels and in normocholesterolemic dogs, and increased fecal excretion of bile acids in hypercholesterolemic cockerels. The data indicate that these insoluble cationic polymers exert their hypocholesterolemic effects by interrupting the enterohepatic circulation of bile acids.

Administration, Oral↗