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Biomedical subjects

D J Howells

Publications and source records attributed to D J Howells.

14 recordsLinked to original sources
PubMed1993

Metabolism of thiodiglycol (2,2'-thiobis-ethanol): isolation and identification of urinary metabolites following intraperitoneal administration to rat.

1. The metabolism of thiodiglycol, 2,2'-thiobis-ethanol, was investigated following i.p. administration to rat. 2. Approximately 90% of the administered dose was excreted in the 0-24-h urine. Four metabolites were isolated by h.p.l.c. and identified by mass spectrometry. Structural assignments were confirmed by comparison with authentic synthetic standards. 3. Thiodiglycol sulphoxide was the major metabolite accounting for approximately > or = 90% of the excreted radioactivity following i.p. injection of 13C4, 35S-thiodiglycol. Thiodiglycol sulphone, S-(2-hydroxyethylthio)acetic acid and S-(2-hydroxy-ethylsulphinyl)acetic acid were identified as minor metabolites. 4. Analysis for thiodiglycol by GC-MS indicated approximately 0.5-1% of the applied dose was excreted unmetabolized.

Animals↗
PubMed1993

Biological fate of sulphur mustard (1,1'-thiobis(2-chloroethane)): uptake, distribution and retention of 35S in skin and in blood after cutaneous application of 35S-sulphur mustard in rat and comparison with human blood in vitro.

1. During the 6-h occluded cutaneous application of 35S-sulphur mustard vapour to rat, most of the dose, approximately 75%, passed through the skin and was systemically-distributed. Up to 25% of the 35S was retained in the skin, up to 30% was excreted in the urine and 5-8% was present in the blood, by the end of the application. 2. 35S initially declined rapidly in skin and then more slowly with a half-life of approximately 7.4 days. Some of the early loss was as sulphur mustard vapour from a possible depot of this compound which was larger with increase in dose. There was some apparent continuing uptake from such a depot into the systemic circulation. 3. The decline of 35S in blood was much slower than that from skin. About one-fifth of the original post-exposure level in the blood still present 6 weeks later. 4. The 35S in blood was mainly in the red cell contents as reaction products of haemoglobin with sulphur mustard. Its persistence in the systemic circulation, after an initial rapid decline due to its removal from the plasma, reflected the 65 day life span of these cells. Significant levels of 35S were found in the plasma only for a few days (t1/2 = 2.4 days). 5. Uptake and subsequent distribution of 35S in rat and human blood in vitro during gradual exposure to 35S-sulphur mustard using a novel method were similar. 35S in the red cells was associated mainly with the haemoglobin protein, but slightly greater binding with human, rather than with rat, plasma components was indicated.

Administration, Cutaneous↗
PubMed1992

Biological fate of sulphur mustard, 1,1'-thiobis(2-chloroethane): isolation and identification of urinary metabolites following intraperitoneal administration to rat.

1. The metabolism of sulphur mustard, 1,1'-thiobis(2-chloroethane), in vivo was investigated following i.p. administration to rat. 2. Approx. 60% of dose was excreted in the 24 h urine. Many metabolites were present; nine have been isolated by h.p.l.c. and characterized by mass spectrometry. Structural assignments were confirmed by comparison with authentic synthetic standards. 3. Some metabolites result from initial hydrolysis of the sulphur mustard, but the majority are formed by conjugation with glutathione. These are further metabolized to N-acetylcysteine conjugates, or to methylthio/methylysulphinyl derivatives by a pathway probably involving beta-lyase, accompanied by oxidation of the mustard sulphur atom to sulphoxide or sulphone. 4. Thiodiglycol sulphoxide, 1,1'-sulphonylbis[2-S(N-acetylcysteinyl)ethane] and 1,1'-sulphonylbis[2-methylsulphinyl)ethane] or 1-methylsulphinyl-2-[2-(methylthio ethylsulphonyl]ethane were the most prevalent metabolites resulting from the three major pathways. Metabolic pathways for the formation of the excretion products are proposed.

Animals↗
PubMed1992

Biological fate of sulphur mustard (1,1'-thio-bis(2-chloroethane)): urinary and faecal excretion of 35S by rat after injection or cutaneous application of 35S-labelled sulphur mustard.

1. A technique for the quantitative cutaneous application of sulphur mustard vapour is described. The maximum rate of uptake of the agent vapour by shaved rat skin in vivo was estimated as 7 micrograms/cm2 per min. 2. The major route of excretion was through the kidneys: greater than 70% of the radioactivity of all doses was excreted in 3 days after either i.v. or i.p. injections of 35S-labelled sulphur mustard, but less (50-70% depending on dose) was excreted in the same time following cutaneous application. 3. This urinary excretion of 35S had a half-life of 1.4 days, and the decreased proportion of the applied dose excreted following cutaneous application may be accounted for by retention of radioactivity in the skin. 4. The contribution of faecal excretion was greater following cutaneous application.

Administration, Cutaneous↗
PubMed1989

In vitro evaluation of a cyanoacrylate bonding agent.

A new cyanoacrylate adhesive developed for orthodontic use was subjected to a controlled in vitro trial of ultimate shear bond strength. Performance deteriorated on storage in saline, rendering the material unsuitable for clinical use. Other alternatives to conventional acid-etch retained composite resin bonding agents are discussed.

Adhesives↗
PubMed1985

The validity and reliability of ratings of dental and facial attractiveness for epidemiologic use.

A method to obtain indices of dental and facial attractiveness for epidemiologic survey work has been evaluated. A two-person panel was constituted to make ratings of photographic records under standardized conditions by means of a visual analogue recording scale. The method proved to be convenient and rapid in operation and its validity was upheld. Good reliability was established and there is scope for further improvement by increasing the size of the panel.

Adult↗
PubMed1966

Observations on the biosynthesis of thiamine in yeast.

1. Methods are described for the isolation of radioactively pure thiamine from yeast and its degradation on a small scale to its cyclic components. 2. A degradation of the pyrimidine ring and a thin-layer method for the separation of thiamine, its derivatives and pyrimidine and thiazole residues are described. 3. [(14)C]Formate is more effectively incorporated into the pyrimidine residue than into the thiazole residue, whereas the reverse is true with l-[Me-(14)C]methionine. 4. Experiments with [Me-(14)C,(35)S]methionine demonstrate that methionine provides an intact unit for the biosynthesis of the thiazole ring. 5. [6-(14)C]Orotic acid is insignificantly incorporated into the pyrimidine residue of thiamine. 6. Experiments with [1-(14)C]- and [2-(14)C]-acetate indicate that it is incorporated as a unit into the thiazole residue, but that only C-2 is incorporated into the pyrimidine residue. 7. l-[U-(14)C]Alanine is also effectively incorporated into the thiazole residue. 8. These results are discussed in relation to possible pathways of biosynthesis of the two ring components of the thiamine molecule.

Acetates↗
PubMedDate not supplied

Biological fate of sulfur mustard, 1,1'-thiobis(2-chloroethane). Urinary excretion profiles of hydrolysis products and beta-lyase metabolites of sulfur mustard after cutaneous application in rats.

The urinary excretion profiles of some metabolites of sulfur mustard were determined by gas chromatography/mass spectrometry after cutaneous application of sulfur mustard in rats. Excretion profiles of the individual metabolites thiodiglycol and thiodiglycol sulfoxide, derived from the hydrolysis of sulfur mustard, were determined in different groups of three rats. Concentrations of thiodiglycol detected increased up to 10 fold after treatment of the urine with hydrochloric acid, presumably because of the excretion of acid-labile esters of thiodiglycol. Free thiodiglycol, free plus esterified thiodiglycol, and thiodiglycol sulfoxide excreted over 8 days accounted for less than 0.3%, 1-1.5%, and 3.4-4.3%, respectively, of the applied dose of sulfur mustard. In a further study, a modified analytical method was applied to determine these hydrolysis products and their acid-labile esters as the single analyte thiodiglycol, after treatment with acidic titanium trichloride. The excretion profile of the combined hydrolysis products was compared with the excretion profile of a different group of metabolites of sulfur mustard derived from the glutathione/beta-lyase pathway. These were also reduced to a common analyte, 1,1'-sulfonylbis-[2-(methylthio)ethane], after similar treatment with titanium trichloride. Urinary excretion of hydrolysis products determined in 4 rats over 8 days accounted for 3.7-13.6% of an applied cutaneous dose of sulfur mustard. Urinary excretion of beta-lyase metabolites accounted for 2.5-5.3% of the applied dose in the same group of rats. The excretion of beta-lyase products showed a much sharper decline than was observed for the hydrolysis products of sulfur mustard.

Administration, Cutaneous↗