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Biomedical subjects

D A Cowan

Publications and source records attributed to D A Cowan.

12 recordsLinked to original sources
PubMed1992

Biotechnology of the Archaea.

The Archaea, designated since 1979 as a separate Super-Kingdom (the highest taxonomic order), are a highly novel group of microorganisms which look much like bacteria but have many molecular and genetic characteristics that are more typical of eukaryotes. These unusual organisms can be conveniently divided according to their 'extreme' environmental niche, into three broad phenotypes: the thermophiles, methanogens and extreme halophiles. Each group has unique biochemical features which can be exploited for use in the biotechnological industries. The extreme molecular stability of thermophile enzymes, the novel C1 pathways of the methanogens and the synthesis of organic polymers by some halophiles are all currently or potentially valuable examples of the biotechnology of the Archaea.

Archaea↗
PubMed1992

Possible indices for the detection of the administration of dihydrotestosterone to athletes.

Dihydrotestosterone (DHT) can be used by an athlete as an anabolic steroid to evade the current International Olympic Committee approved drug tests. To investigate the possibility of a method for its detection, the heptanoate ester of DHT was administered to two male subjects (150 mg i.m.). Urine samples, collected before and after the injection, were subjected to enzymatic hydrolysis and the excretion rates of DHT, 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol) and testosterone (T) were determined by radioimmunoassay. Relative changes in the excretion of DHT, 3 alpha-diol, 5 alpha-androstane-3 beta,17 beta-diol (3 beta-diol), 5 beta-androstane-3 alpha, 17 beta-diol (5 beta-diol), T and epitestosterone (17 alpha hydroxyandrost-4-en-3-one; Epi-T) were determined by gas chromatography-mass spectrometry (GC-MS). Following administration of DHT, the urinary excretion rates of DHT, 3 alpha-diol and 3 beta-diol increased when compared to those of T, Epi-T, 5 beta-diol and luteinizing hormone (LH). Concentrations of DHT in the plasma increased whereas those of T, LH and follicle stimulating hormone decreased. The changes following such modest doses of DHT suggest that these ratios of urinary hormones may be used for the detection of doping with DHT.

Adult↗
PubMed1992

Peptide hormones and sport: misuse and detection.

In 1989 the Medical Commission of the International Olympic Committee (IOC) introduced the new doping class of 'peptide hormones and analogues,' which include human chorionic gonadotrophin (hCG) and related compounds, adrenocorticotrophic hormone (ACTH), human growth hormone (hGH), all the releasing factors of these listed hormones, and erythropoietin (Epo). Currently there are no IOC approved definitive tests for these hormones but highly specific immunoassays combined with suitable purification techniques may be sufficient to warrant IOC approval. The importance of measuring hCG and luteinizing hormone (LH) in the control of testosterone misuse is discussed and strategies for the detection of hGH, ACTH and Epo administration are suggested.

Adrenocorticotropic Hormone↗
PubMed1992

Enzymes from thermophilic archaebacteria: current and future applications in biotechnology.

The one guaranteed property of enzymes isolated from extremely thermophilic micro-organisms is their thermostability. Most significantly, almost any such enzyme will be more thermostable than the functionally similar enzyme from a lower temperature source. Thermostability is not an isolated property: resistance to heat denaturation imparts stability to a number of other denaturing influences (detergents, organic solvents, etc). These characteristics of hyperthermophilic enzymes are the most likely basis for the development of new biotechnological applications. A limited number of hyperthermophilic enzymes have found application in specialist biotechnological applications; others have visible potential in growing areas of biotechnology. Existing and potential applications are discussed using DNA manipulation enzymes, dehydrogenases, and esterases as examples.

Archaea↗
PubMed1991

Human chorionic gonadotrophin and sport.

Human chorionic gonadotrophin (hCG) is a glycoprotein hormone which is produced in large amounts during pregnancy and also by certain types of tumour. The biological action of hCG is identical to that of luteinizing hormone, although the former has a much longer plasma half-life. Some male athletes use pharmaceutical preparations of hCG to stimulate testosterone production before competition and/or to prevent testicular shutdown and atrophy during and after prolonged courses of androgen administration. Testosterone administration can be detected by measuring the ratio of concentrations of testosterone to epitestosterone (T/E). An athlete is often considered to have failed a drug test if the urinary T/E ratio is greater than 6. In contrast, hCG administration stimulates the endogenous production of both testosterone and epitestosterone without increasing the urinary T/E ratio above normal values. Although the administration of hCG was banned by the International Olympic Committee (IOC) in 1987, no definitive test for hCG has been approved by the IOC. Currently, the only way of measuring small concentrations of hCG is by immunoassay, and this does not have a discriminating power as great as gas-liquid chromatography with mass-spectrometry which is necessary to satisfy IOC requirements. Extraction procedures and chromatographic steps could be introduced before using a selected immunoassay for hCG to meet these requirements.

Chorionic Gonadotropin↗
PubMed1991

Effect of administration of human chorionic gonadotrophin on criteria used to assess testosterone administration in athletes.

Abnormal ratios of testosterone to epitestosterone (T/E) and testosterone to LH (T/LH) in the urine of male athletes are indicative of testosterone administration. The T/E ratio has been adopted by the International Olympic Committee as the sole criterion used in the detection of testosterone administration. An athlete is usually considered to have failed a drug test if the urinary T/E ratio is greater than 6. Human chorionic gonadotrophin (hCG) has been used by some male athletes to stimulate testicular secretion of testosterone. The purpose of this investigation was to examine whether the urinary T/E ratio can remain unaffected by administration of hCG to normal adult males. Administration of hCG resulted in large increases in serum testosterone concentrations and urinary T/LH ratios but small changes in urinary T/E ratios of two subjects (maximum T/E values observed were 0.8 and 1.2 respectively). These observations suggest that the urinary T/LH ratio is a valuable indicator of hCG as well as of testosterone administration. This study is the first to measure urinary T/LH ratios using the technique of gas chromatography-mass spectrometry for quantification of testosterone, and highly specific monoclonal antibodies for the measurement of LH. An ultrafiltration method is proposed as part of a confirmatory procedure to be adopted in the measurement of urinary gonadotrophins for drug control in sport.

Chorionic Gonadotropin↗
PubMed1990

Criteria to indicate testosterone administration.

A detection method for testosterone administration was developed using radioimmunoassay to measure the urinary ratios of testosterone (T) to epitestosterone (E) and to luteinizing hormone (LH). A comparative study of the effect on these ratios of a single intramuscular injection of testosterone heptanoate followed by stimulation with human chorionic gonadotrophin (HCG) in three normal men was undertaken. To allow immediate investigation, a commercially supplied epitestosterone antiserum was used. This study showed that both T/E and T/LH ratios could be used to detect testosterone administration, the latter also being an indicator of HCG use due to cross-reactivity with the LH antiserum. Subsequently, an epitestosterone antiserum of superior specificity was raised and used in a study to demonstrate the insignificant effect of exercise on these ratios. Finally, an intramuscular injection of a combined preparation of testosterone/epitestosterone heptanoates resulted in raised ratios of T/LH but not of T/E. This demonstrated the importance of the T/LH ratio in circumstances where the T/E ratio can be easily circumvented.

Adult↗
PubMed1978

Metabolic N-oxidation of 3-substituted pyridines: identification of products by mass spectrometry.

The mass spectral characteristics of the N-oxides of a range of 3-substituted pyridines, and of quinoline and isoquinoline, are described. The molecular ion is the base peak in the majority of cases, provided that thermolysis is minimized when using the direct probe or gas chromatography inlets. Chromatographic and mass spectral evidence is presented which indicates that biological oxidation of the heteroaromatic nitrogen of 3-substituted pyridines is a route of metabolism in vivo and in vitro.

Animals↗
PubMed1976

Identification of four new metabolic products of metoclopramide using mass spectrometry.

1. N-(Diethylaminoethyl)-4-amino-5-chloro-2-methoxybenzamide (metoclopramide, I) N-(ethylaminoethyl)-4-amino-5-chloro-2-methoxybenzamide (II), N-(aminoethyl)-4-amino-5-chloro-2-methoxybenzamide (III), N-(2'-hydroxyethyl)-4-amino-5-chloro-2-methoxybenzamide (IV), N-(diethylaminoethyl)-4-amino-5-chloro-2-hydroxybenzamide (V) and N-(ethylaminoethyl)-4-amino-5-chloro-2-hydroxybenzamide (VI) were obtained from chloroform extracts of incubation mixtures of I or II (HCl salts) with 9000 g liver microsomal preparations from male rabbits.

Animals↗
PubMed1975

Metabolism of phenothiazines: identification of N-oxygenated products by gas chromatography and mass spectrometry.

The solid inlet mass spectra of the N-oxide and N-oxide sulphoxide metabolites of promazine, chlorpromazine and methotrimeprazine have been determined at different temperatures and compared with the mass spectra of the main thermolytic product of the N-oxides and N-oxide sulphoxides obtained during combined gas chromatography-mass spectrometry. Diagnostic ions were produced by direct insertion of the compounds at ambient temperature into the mass spectrometer. These ions distinguish the N-oxides of arylalkyl tertiary amines from the N-oxygenated derivatives of primary and secondary arylalkylamines.

Chlorpromazine↗