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Biomedical subjects

A E Theobald

Publications and source records attributed to A E Theobald.

12 recordsLinked to original sources
PubMed2001

Structure-activity investigation of the inhibition of 3-hydroxypyridin-4-ones on mammalian tyrosine hydroxylase.

3-Hydroxypyridin-4-ones are currently one of the main candidates for the development of orally active iron chelators. Small bidentate ligands tend to inhibit iron-containing metalloenzymes and therefore can cause undesirable side effects. A range of 3-hydroxypyridin-4-ones with different R2 substituents was selected for the investigation of the structure-activity relationship between the chemical nature of the ligand and the inhibition of mammalian tyrosine hydroxylase. Results indicated that lipophilicity was the dominant factor in controlling the ability of this class of chelator to inhibit mammalian tyrosine hydroxylase. Ligands with hydrophilic R2 substituents tended to be weak inhibitors. No significant correlation was found in this study between iron-binding affinity, extended R2 chain length, and enzyme inhibitory activity. In contrast, both the LogP values of the entire molecule and of the R2 segment correlated well with inhibitory activity.

Animals↗
PubMed2001

In-vitro activity of S. lavandulaefolia (Spanish sage) relevant to treatment of Alzheimer's disease.

Salvia lavandulaefolia Vahl. (Spanish sage) essential oil and individual monoterpenoid constituents have been shown to inhibit the enzyme acetylcholinesterase in-vitro and in-vivo. This activity is relevant to the treatment of Alzheimer's disease, since anticholinesterase drugs are currently the only drugs available to treat Alzheimer's disease. Other activities relevant to Alzheimer's disease include antioxidant, anti-inflammatory and estrogenic effects. Results of in-vitro tests for these activities are reported here for S. lavandulaefolia extracts, the essential oil and its major constituents. Antioxidant activity (inhibition of bovine brain liposome peroxidation) was found in the EtOH extract of the dried herb (5 mg mL(-1)) and the monoterpenoids (0.1 M) alpha- and beta-pinene and 1,8-cineole. Thujone and geraniol had lower antioxidant effects, while camphor had no antioxidant effects. Possible anti-inflammatory activity (eicosanoid inhibition in rat leucocytes) was found in the EtOH extract (50 microg mL(-1)) and was shown by the monoterpenoids alpha-pinene and geraniol (0.2 mM), but not 1,8-cineole, thujone or camphor. Possible estrogenic activity (via induction of beta-galactosidase activity in yeast cells) was found in the essential oil (0.01 mg mL(-1)) and the monoterpenoid geraniol (0.1-2 mM). 1,8-Cineole, alpha- and beta-pinene and thujone did not exhibit estrogenic activity in this analysis. These results demonstrate that S. lavandulaefolia, its essential oil and some chemical constituents have properties relevant to the treatment of Alzheimer's disease and provide further data supporting the value of carrying out clinical studies in patients with Alzheimer's disease using this plant species.

Alzheimer Disease↗
PubMed1990

Structure-distribution relationship studies of 99mTc-2,3-diamine complexes.

In order to develop an organ specific radiopharmaceutical a structure-distribution relationship study was carried out in mice using a homologous series of cationic 99mTc-2,3-diaminoalkanes. The results showed that specific organ uptakes were uniformly low, generally less than 5% of the injected dose. Rapid removal of the lower homologues from the circulation through the excretory organs and an excessive blood retention of the higher homologue complexes were observed. Evidence of preferential renal clearance (over the hepatobiliary clearance) by the complexes was obtained from both linear and multiple regression analyses. Using the combined biodistribution data for the cationic diamino complexes and the equivalent anionic 99mTc-2,3-dioximinoalkane complexes, the multiple correlation was evaluated between the % urinary tract uptake data at 4 h post injection and a combination of log P, molecular diameter and charge (+1 or -1) of the complexes. From the magnitude and sign of the coefficients in the equation for the regression line, it was found that the dependence of the amount of complex cleared renally on the physico-chemical parameters tested is in the order; log P, cationic charge and molecular diameter.

Animals↗
PubMed1990

Structure-distribution relationship studies of 99mTc-2,3-dioxime complexes.

The structure-distribution relationship studies of a homologous series of anionic 99mTc-2,3-dioximinoalkanes in mice, showed very low specific organ uptakes due to a combination of rapid clearance and excessive blood binding factors as found for the cationic 99mTc-diamine analogues (Salako and Theobald, Nucl. Med. Biol. 17, 437-441; 1990. The dioxime complexes showed a preference for hepatobiliary clearance unlike the diamine complexes which were cleared through the renal tract. The relationship between the amount cleared through the biliary tract and molecular weight of the dioxime complexes is binomial, with the optimum about the C-8 chain homologue. The hepatobiliary clearance model which was discovered for these complexes follows a multiple correlation equation which has a combination of four physico-chemical properties in the order: log P, charge, protein binding and molecular weight. It was observed particularly that the log P and charge have broadly similar magnitudes (to those in the urinary model of the diamine complexes) but reversed signs. The sign on the charge coefficient is negative, indicating that an overall negative charge is required for efficient hepatobiliary extraction and excretion of these Tc-complexes.

Animals↗
PubMed1987

Determination of ionisation constants of radiopharmaceuticals in mixed solvents by HPLC.

The uptake of some ionogenic radiopharmaceuticals may be explained on the basis of a pH shift theory. An HPLC method for pKa measurement has been developed for radiotracers. It has been tested with several amines and used to estimate the pKsa (pKa in the mixed solvent 30% acetonitrile-water) of some 99mTc-PnAO complexes by observing the change in capacity factor k' with change in mobile phase pH. The non-ionogenic complexes Tc-PnAO and Tc-DE-PnAO showed constant k' values while the ionogenic complexes Tc-MNE-PnAO and Tc-IP-PnAO had pKsa values of about 6.6 and 8.3. The method is reproducible and is applicable to nearly all ionogenic radiopharmaceuticals.

Chromatography, High Pressure Liquid↗
PubMed1978

Multiple-scored tablets. Weight and content uniformity of subdivisions and distribution of active constituent within and between tablets.

Using three brands of multiple-scored levodopa tablets, B.P. (500 mg) and one brand of sulphamethoxypyridazine tablets B.P. (500 mg) the weight and content uniformity of the subdivisions has been examined. It is shown that quartering of such tablets can result in subunits which do not conform to recognized standards of weight uniformity, and in some instances content uniformity may be questionable. The homogeneity of distribution of active constituent between tablets has been determined and compared with that within tablets (between quarters of individual tablets). Statistical evaluation of the results is presented.

Drug Compounding↗