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Biomedical subjects

S C Mitchell

Publications and source records attributed to S C Mitchell.

At least 55 records · Page 3Linked to original sources
PubMed1996

Human metabolism of paracetamol (acetaminophen) at different dose levels.

Urine (0-24 h) was collected from five subjects on separate occasions following the ingestion of paracetamol at five different dose levels (500, 750, 1000, 1250, 1500 mg) which spanned the normal therapeutic range. The major urinary metabolites were sulphuric and glucuronic acid conjugates which together accounted for around 50% of the administered dose. Unchanged paracetamol excretion was low (5-20%). This situation was similar over the entire dose range. These findings are discussed in relation to previous single dose studies reported in the literature.

Acetaminophen↗
PubMed1996

Sparteine metabolism in a Nigerian population.

The oxidative metabolism of sparteine has been investigated in a Nigerian population. The distribution of metabolic capacities was shown to be skewed with two subjects (2/97, 2.1%) being relatively deficient in their ability to produce the dehydrometabolites. These observations afford evidence that sparteine oxidation is under polymorphic control in Nigerians.

Adult↗
PubMed1996

Rôle of bile in the elimination of dipropyl sulphone from the male rat.

Following oral administration of [35S]-dipropyl sulphone to male Wistar rats (4.24 mmol/kg body wt), the only radioactive component subsequently found in the blood and bile was the sulphone. Biliary excretion played an important rôle in the elimination of this compound, with 16% of the dose excreted during the first twenty-four hours and 33% passing through the bile duct over a two day period. Bile/plasma concentration ratios remained constant during the first day (c. 46-fold), suggesting that a concentration process was taking place and that active transport of this low molecular weight compound (150 Da) into the bile was occurring.

Animals↗
PubMed1996

Discontinuous distribution of N-oxidation of dietary-derived trimethylamine in a British population.

1. Whilst the majority of individuals within a British white population are able to convert > 90% of their dietary-derived trimethylamine to its N-oxide, outliers exist who show varying degrees of decreased metabolism. Such individuals, excrete unoxidized trimethylamine in their urine and, if N-oxidation is sufficiently low, may experience malodour problems (Fish-Odour syndrome). 2. Such observations have now been extended to a much larger group (n = 421; 221 males) of British white volunteers recruited from staff and students of Imperial College Medical School at St. Mary's, London. Each subject collected a 0-24-h urine sample, which was subsequently analysed for total trimethylamine and trimethylamine N-oxide content. 3. Sixteen subjects (3.8% population; seven male, nine female) excreted < 90% of their total trimethylamine output as N-oxide. All six subjects who excreted < 80% as N-oxide (indicative of potential heterozygous status for deficient N-oxidation-fish odour syndrome) were female.

Adult↗
PubMed1995

Dimethylamine in human urine.

The urinary excretion of dimethylamine has been measured in 203 unrelated healthy volunteers (102 male) who maintained their normal diets. The results for female volunteers are the first reported in the literature. The average daily output was 17.43 +/- 11.80 mg (mean +/- S.D.) (21.21 +/- 14.78 male; 13.74 +/- 5.65 female) with values for the majority of the population lying within the 0.68-35.72 mg range. Four male outliers excreted up to 109.2 mg; these large amounts of dimethylamine were presumed to be of dietary origin. The literature pertaining to urinary levels of dimethylamine has been summarised and integrated with the present observations.

Adult↗
PubMed1995

A subgroup of LHRH neurons in guinea pigs with progestin receptors is centrally positioned within the total population of LHRH neurons.

Although the role of gonadal steroids in inducing the LH surge is undisputed, the mechanism(s) whereby steroids induce the release of the hypothalamic luteinizing hormone-releasing hormone (LHRH) remain(s) enigmatic. In this study we examined the issue of the presence of steroid receptors in LHRH neurons using a mammalian species that has a true luteal phase, namely, guinea pigs. Progestin receptors (PR) were localized in LHRH neurons of ovariectomized guinea pigs administered estradiol (10-20 micrograms estradiol benzoate) for 3-4 days, using several different immunocytochemical protocols. The subgroup of LHRH neurons containing PR, although small, was strategically positioned within the core of the total population of LHRH neurons. This central position was visualized in simultaneous views of three-dimensional computer reconstructions of the populations of LHRH/PR neurons and LHRH neurons. The subgroup of LHRH/PR neurons formed a thread permeating the population of LHRH neurons. We propose that in guinea pigs, LHRH neurons containing progestin receptors, are foci of activity, capable of activating a larger component of the LHRH population of cells in certain endocrine conditions, such as prior to the LH surge.

Animals↗
PubMed1995

Distribution of dipropyl [35S]-sulphoxide in the rat.

Dipropyl [35S]-sulphoxide was administered by gavage (4.24 mmol/kg body weight) to adult male Wistar rats and the placement of radioactivity about the animal examined at 4, 8 and 12 hours post-dosing. Widespread and diffuse distribution throughout soft tissues was observed with the largest amounts of radioactivity being found within the liver (3.2% dose at 4 h) and kidney (1.3% dose at 4 h). Activity levels declined over the 12 hour experimental period. This distribution pattern is discussed and compared with results previously reported for dimethyl sulphoxide.

Animals↗
PubMed1995

Fate of dipropyl sulphone in rat.

1. Dipropyl [35S]-sulphone was administered by gavage (4.24 mmol/4 ml/kg body weight) to the adult male Wistar rat following an overnight fast. 2. Urine was the major route of excretion (83%) with more radioactivity appearing during the second day (47%) than the first (28%). Only small amounts were found in the faeces (10%). Biliary excretion played an important role with substantial amounts of the dose (33%) passing through the bile duct during 0-48 h. A near total recovery was achieved suggesting that only small amounts (2%) may have been lost as volatile components. 3. Metabolism was limited, the majority (> or = 98%) of the sulphone being recovered unchanged. Oxidation of the sulphur with the formation of inorganic sulphate was the only pathway observed.

Animals↗
PubMed1994

Effectiveness of a calculus scaling gel.

This study evaluated the effect of a calculus scaling gel (SofScale) on time and ease of the scaling procedure in a double-blind, split-mouth clinical study of 32 subjects. The Volpe-Manhold calculus index was used to quantify the distribution and amount of calculus deposition on the lingual aspect of the mandibular 6 anterior teeth at baseline. The gel was applied directly to the calculus and subgingivally to the area to be scaled. Pre- and post-treatment gingival and stain indices were taken. Operator and subject questionnaires were completed immediately after treatment to determine ease of the scaling procedure. Results were analyzed with paired t-tests. The time difference in scaling between the product and placebo side was not significant. This study found that SofScale is safe to gingival tissues and does not promote tooth sensitivity. However, this study did not find significant differences in scaling time between product and placebo when using a 2-minute gel contact time.

Adolescent↗
PubMed1994

The toxicity of phenothiazine.

Phenothiazine, the parent compound of a multitude of present-day drugs, has been employed on an extensive scale for its insecticidal, fungicidal, antibacterial and anthelmintic properties. Almost a catholicon, its widespread use in animals and man has led to the uncovering of many adverse reactions encompassing effects on blood elements, neuromuscular problems and photosensitization. The high lipophilicity of phenothiazine and the formation of two redox systems amongst its many metabolites can facilitate the occurrence of generalised macromolecular disruption. Information from the literature has been garnered and appraised in this review to enable an insight into the possible mode(s) of interaction of phenothiazine with living systems.

Animals↗
PubMed1994

Fate of dimethylamine in rat and mouse.

1. [U-14C]-dimethylamine hydrochloride was administered by gavage (20 mumol/kg body weight) to adult male Wistar rat and CD1 strain mouse. 2. In both species, urine was the main route of excretion with the majority of radiolabel (91%) being voided during the first day. Additional small amounts of radioactivity were detected in the 24-72 h urine (2%), in faeces (2%) and amidst exhaled air (1%), with minor amounts remaining within the carcass (1%) after 3 days. 3. Metabolism was limited to demethylation, with the majority of the compound (89% dose; 96% urinary radioactivity) being excreted unchanged.

Animals↗
PubMed1994

Fate of dipropyl sulphide and dipropyl sulphoxide in rat.

1. Dipropyl [35S]-sulphide and dipropyl [35S]-sulphoxide were administered by gavage (4.24 mM/4 ml/kg body wt) to adult male Wistar rats following an overnight fast. 2. Urine was the major route of excretion for both compounds, with more radioactivity appearing during the second day (c. 43%) than the first (c. 26%). Only small amounts were found in the faeces (c. 5%). Biliary excretion played an important role with substantial amounts of the dose (c. 25%) passing through the bile duct during 0-48 h. Following ingestion of the sulphide large quantities of radioactivity (18%) were detected in exhaled air. Near total recoveries were achieved for both compounds, although 13% of the radioactivity remained within the carcass 3 days after administration of the sulphoxide. 3. Absorption and elimination half-lives were in the region of 5 and 8 h, respectively, for both compounds, with the sulphoxide plasma profile showing a prolonged plateau region. 4. Metabolism was limited to oxidation of the sulphur with the formation of the sulphoxide and sulphone, and trace amounts of inorganic sulphate.

Animals↗
PubMed1994

Fate of dimethylamine in man.

1. The fate of [14C]-dimethylamine was investigated following oral administration to four male volunteers. 2. The major route of excretion was urine, with 94% of the administered radioactivity being voided over 3 days (87% during the first 24 h). Small amounts (1-3%) of radioactivity were found in the faeces and expired air. 3. Metabolism was limited with only 5% being demethylated to methylamine. The remainder of the dose was excreted unchanged. 4. Pharmacokinetic studies indicated rapid (t1/2ab = 8 min) and extensive absorption (bioavailability = 82%) from the gastrointestinal tract followed by widespread distribution and a fairly prompt excretion (t1/2el = 6-7 h) with a plasma clearance of 190 ml/min.

Administration, Oral↗
PubMed1993

The fish odour syndrome: biochemical, familial, and clinical aspects.

OBJECTIVES: To study the biochemical, familial, and clinical features of the fish odour syndrome among subjects with suspected body malodour. DESIGN: Subjects who responded to a newspaper article were screened for the fish odour syndrome by interview and biochemical tests. Families of subjects with the syndrome were tested if possible. SETTING: St Mary's Hospital, London, and some interviews at subjects' homes. SUBJECTS: 187 subjects (28 males) with suspected body malodour, of whom 156 (19 males) underwent biochemical tests. Five families of six of the subjects with the fish odour syndrome agreed to further tests. MAIN OUTCOME MEASURES: Amounts of trimethylamine and trimethylamine N-oxide in urine collected over 24 hours under normal dietary conditions and for eight hours after oral challenge with 600 mg trimethylamine. RESULTS: The fish odour syndrome was diagnosed in 11 subjects: the percentage of total trimethylamine excreted in their urine samples that was oxidised to trimethylamine N-oxide was < 55% under normal dietary conditions and < 25% after oral challenge with trimethylamine (in normal subjects > 80% of trimethylamine was N-oxidised). Parents of six of the subjects with the syndrome were tested: all showed impaired N-oxidation of excreted trimethylamine (< 80%) after oral challenge, indicating that they were heterozygous carriers of the allele for the syndrome. The syndrome was associated with various psychosocial reactions including clinical depression. CONCLUSIONS: The fish odour syndrome can be inherited in an autosomal recessive fashion. It should be considered as a possible causative factor in patients complaining of body malodour.

Adolescent↗