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Biomedical subjects

S F Cooper

Publications and source records attributed to S F Cooper.

At least 19 recordsLinked to original sources
PubMed1997

Effect of estradiol on the induction of porphyria by hexachlorobenzene in the rat.

Hexachlorobenzene (HCB) is porphyrinogenic in adult female but not in male rats. This study aimed to assess the role of 17beta-estradiol in the induction of porphyria by HCB in both sexes by adding or removing the hormone. Groups of intact females, ovariectomized females (Ova), castrated males (Cas), and Cas receiving 17beta-estradiol (4 mg/kg, i.m., once a week beginning 2 weeks prior to HCB) were given five consecutive daily doses of HCB (100 mg/kg in corn oil, p.o.). Porphyria was assessed by urinary uroporphyrin excretion measured at days 16, 31, 38, 45, 52, 59, and 87. The percentage of porphyric rats in intact females increased from day 31 (58%) to day 87 (75%), whereas none of the Ova or Cas rats responded. However, administration of estradiol (days 120-169) and another sequence of HCB doses (days 134-138) to the same Ova rats caused porphyria (50% at day 186). Cas rats given estradiol also developed porphyria (43 and 86% on days 31 and 87, respectively). HCB-treated Ova rats given two doses of estradiol at either days 1 and 8 or days 22 and 29 developed a porphyria of similar magnitude (day 52). The role of estradiol cannot be explained by a reduction of pentachlorothiophenol formation, a putative detoxication pathway. Overall, results show that both sexes have the ability to respond to HCB when 17beta-estradiol is present and suggest that the sexual dimorphism in HCB-induced porphyria in the rat is related to the hormonal status.

Animals↗
PubMed1995

Enantioselective determination of oxprenolol and its metabolites in human urine by cyclodextrin-modified capillary zone electrophoresis.

A stereospecific capillary electrophoresis assay for oxprenolol enantiomers and their basic metabolites in human urine has been developed using hydroxypropyl-beta-CD as a chiral selector in the mobile phase. The bioassay method has been validated and the detection limit from spiked urine samples is 0.2 micrograms/ml. The calibration curves are linear from 0.4 to 16 micrograms/ml. Extraction recovery ranged from 84.7 to 96.4% for all the compounds studied. The influence of various parameters on the chiral separation of oxprenolol and its basic metabolites have been investigated. Urinary excretion profiles of oxprenolol enantiomers and those of two metabolites have also been studied, following a single oral dose of racemic oxprenolol.

Calibration↗
PubMed1995

Determination of the enantiomers of metoprolol and its major acidic metabolite in human urine by high-performance liquid chromatography with fluorescence detection.

Enantiomers of metoprolol and its acidic metabolite H 117/04 were determined in human urine by high-performance liquid chromatography (HPLC) with fluorometric detection after chiral derivatization. The carboxyl functional group of the major metabolite was blocked by esterification after solid-phase extraction, which helped to quantitate this compound from interfering substances. The assay method was validated. The recovery of (-)- and (+)-metoprolol from urine was 86.3-90.5%; and the recovery of the (-)- and (+)-acidic metabolite H 117/04 from urine was 74.4-83.9% at different concentrations.

Adult↗
PubMed1994

Determination of the enantiomers of bunolol in human urine by high-performance liquid chromatography on a chiral AGP stationary phase and identification of their metabolites by gas chromatography-mass spectrometry.

A high-performance liquid chromatographic method using a chiral AGP column was developed to screen and determine the enantiomers of bunolol in human urine. The recovery of (+)- and (-)-bunolol from urine was 91.79-95.23% at different concentrations. The coefficients of variation (C.V.) were less than 2.1 and 2.3% for intra- and inter-assays, respectively. Urinary metabolites were detected using GC-MS after derivatization with N-methyl(trimethylsilyl)trifluroacetamide. The influences of pH and modifier on a chiral AGP column were studied.

Adult↗
PubMed1993

The metabolism of piperidine-type phenothiazine antipsychotic agents. II. Sulforidazine in dog and human.

1. The metabolism of sulforidazine was studied in female dogs and adult male humans after oral administration of 37.5 mg and 25.0 mg, respectively. 2. Metabolites in organic extracts of dog urine were separated by h.p.l.c. and individually collected prior to mass spectrometric analysis, while organic extracts of human urine were directly subjected to plasmaspray h.p.l.c.-mass spectrometric determination. In the case of phenolic metabolites, the urinary extracts from both species were derivatized with a silylating reagent (with or without prior enzymic hydrolysis) and subsequently analysed by h.p.l.c.-mass spectrometry. The structures of metabolites with the exception of phenols were confirmed by comparison of their mass spectra and chromatographic behaviours with those of authentic standards. 3. The compounds identified in urine of both species were sulforidazine, two diastereomers of sulforidazine ring sulphoxide, the lactam of sulforidazine ring sulphoxide and a phenolic derivative of sulforidazine, whereas sulforidazine N-oxide and the lactam of sulforidazine were identified only in human urine. Moreover the phenolic metabolite was present in human urine in both unconjugated and conjugated forms, whereas dog urine had only the conjugated form. 4. Sulforidazine and some of its major metabolites were quantified by an h.p.l.c. method. The mean urinary excretions (0-48 h) of sulforidazine were similar in human (n = 3) and dog (n = 3) (5.9 +/- 0.7% and 7.2 +/- 1.9%), as were the excretions of sulforidazine ring sulphoxide (13.2 +/- 4.6% and 13.3 +/- 4.4%), while the lactam of sulforidazine ring sulphoxide was a major metabolite only in human (7.5 +/- 2.8% and < 0.1%). The lactam of sulforidazine was a minor metabolite in human. 5. The metabolites observed in human urine were similar to those previously reported in rat, except that sulforidazine N-oxide was found only in human, whereas the two diastereomers of N-desmethylsulforidazine ring sulphoxide were observed only in rat. These data suggest that rat may be a more suitable animal than dog for further study of the metabolism of the piperidine ring of sulforidazine.

Adult↗
PubMed1992

Determination and identification of amiloride in human urine by high-performance liquid chromatography and gas chromatography-mass spectrometry.

A simple and sensitive high-performance liquid chromatographic method was developed to screen and determine amiloride (I) in human urine. The detection limit of the method is 0.12 micrograms/ml and the recovery of amiloride from urine was 80.4-85.5% at different concentrations. The coefficients of variation were less than 2.8 and 4.4% for intra- and inter-assays, respectively. Total urinary excretion of I in 24 h after oral administration of 5 mg or 15 mg of I ranged from 22.0 to 33.3% of the total dose for three different subjects. I could be detected in urine up to at least 44 h after a 5-mg dose and 72 h after a 15-mg dose. A gas chromatographic-mass spectrometric (GC-MS) confirmatory method was established based on the methanolysis of I to methyl 3,5-diamino-6-chloropyrazine-carboxylate (II). The di-N-trimethylsilyl derivative of II showed very good GC-MS properties and provided reliable structure information for confirmation analysis of I. This is the first time that a reliable GC-MS method has been reported for the detection of urinary I.

Adult↗
PubMed1989

Comprehensive screening procedure for diuretics in urine by high-performance liquid chromatography.

A rapid and reliable screening procedure using high-performance liquid chromatography for the detection of 23 diuretics (belonging to five different pharmacological groups) in urine has been developed. Two aliquots of 2-ml urine samples were extracted separately under acidic and basic conditions. The acidic and basic extracts were pooled, evaporated to dryness and reconstituted in methanol. The methanolic extract was injected onto a Hewlett-Packard Hypersil ODS C18 (5 microns) column (column I) and a Hewlett-Packard LiChrosorb RP-18 (5 microns) column (column II; an alternative column). The same gradient mobile phase was used for both columns. A diode array ultraviolet detector was set to monitor the signal to the integrator (Chem Station) at 230 and 275 nm. Recovery studies of the 23 diuretics were performed under acidic and basic conditions. The overall lower limits for detection on column I using both extraction procedures ranged from 0.5 to 1.5 micrograms/ml of urine (average 1.0 micrograms/ml). Amiloride, ethacrynic acid and probenecid could not be detected below 5 micrograms/ml of urine. No interference from the biological matrix was apparent. Amiloride could be detected in urine 4 h after oral administration of 15 mg of amiloride to a healthy volunteer, when the sample was extracted under alkaline conditions. The suitability of the screening method for the analysis of urine samples was tested by studying the variation with time of chlorthalidone, furosemide, probenecid, acetazolamide, quinethazone, spironolactone, bendroflumethiazide, bumetanide, triameterene and hydrochlorothiazide concentrations in the urine of normal human volunteers after minimum single or multiple (probenecid) doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1982

Gas--liquid chromatographic determination of flurazepam and its major metabolites in plasma with electron-capture detection.

A sensitive and selective gas--liquid chromatographic method, using the electron-capture detector for the quantitative determination of flurazepam and its major blood metabolites is described. After extraction and back-extraction steps, flurazepam (I) is well separated from its main metabolites, N-1-hydroxyethylflurazepam (metabolite II) and N-1-desalkylflurazepam (metabolite III). Metabolite II is quantitated after forming its stable tert.-butyl-dimethylsilyl derivative by reaction with tert.-butyldimethylchlorosilane--imidazole reagent. The procedure permits the rapid and selective routine determination of flurazepam and its metabolites (II and III) in plasma with a detection limit of 3 ng/ml for flurazepam (I), 1 ng/ml for metabolite II and 0.6 ng/ml for metabolite III. The procedure is linear over the range of concentrations encountered after administration of a single oral therapeutic dose. No interference from the biological matrix is apparent. The suitability of the method for the analysis of biological samples was tested by studying the variation with time of flurazepam and its metabolites' plasma concentrations in normal human volunteers after a single, therapeutic 30-mg oral dose of flurazepam.

Chromatography, Gas↗
PubMed1981

A genetic study of the effects of the repair-deficient mei-9a mutation in Drosophila on spontaneous and X-ray-induced paternal sex chromosome loss.

The repair-deficient mutant, mei-9a in Drosophila melanogaster was investigated regarding its effect on spontaneous and X-ray-induced chromosome loss in male postmeiotic cells. From matings of males carrying a mei-9a or an ordinary ring-X and a doubly marked Y chromosome (BSYy+) with mei-9a or ordinary females, the spontaneous frequencies of complete loss, partial loss, and inferred ring-X loss (based on shifts in sex ratio female:male) were significantly higher with mei-9a than with non-mei-9a. When males were given 3000 rad X-irradiation, frequencies of induced partial loss, inferred ring-X loss and the reduction in the number of progeny per female were significantly greater with mei-9a than with non-mei-9a. The results provide evidence that the mei-9a is a potentiator of both spontaneous and X-ray-induced chromosome lesions in sperm of the Drosophila male. Evidence is presented which implicates the presence of mei-9a in the P1 female and not the male as (at least) largely responsible for the characteristic mei-9a effects.

Animals↗
PubMed1981

Genetic study on the effects of the repair-deficient mutant females mei-9a, mei-41D5, mus101D1, mus104D1 and mus302D1 of Drosophila on spontaneous and X-ray-induced chromosome loss in the paternal genome.

The repair-deficient mutants mei-9a, mei-41D5, mus101D1, mus104D1 and mus302D1 in Drosophila melanogaster were investigated regarding their effects on spontaneous and X-ray-induced chromosome loss in postmeiotic cells. Each mutant was incorporated singly into XC2, and the ring-X male provided with BSYy+. From matings of males carrying mus101D1, mus302D1 or mei-41D5, mutants identifying a caffeine-sensitive (CAS) postreplication-repair pathway, with corresponding mutant females, and non-mutant males to non-mutant females, overall frequencies of spontaneous partial loss and spontaneous complete loss were significantly increased in each mutant cross except for spontaneous complete loss with mus302 where an increase was noted only in brood 2. Similar findings were noted when males carrying the excision-repair mutant mei-9a were mated with mei-9a females. Males carrying the mutant mus104D1, identifying a caffeine-insensitive (CIS) postreplication-repair pathway, tested with mus104D1 females, produced results that were not significantly different from non-mutant controls. When males were given 3000 rad X-irradiation, frequencies of induced partial loss were significantly higher with mus101D1, mus302D1, mei-41D5 and mei91, and not significantly higher with mus101D1, mus302D1, mei41D5 and mei-9a, and not significantly different from controls with mus104D1. It was suggested that the functional CAS postreplication-repair pathway primarily promotes repair of breaks while an alternative pathway(s) not defined by mus104 promotes misrepair. Therefore, the significant increases in both spontaneous and induced partial loss with the excision-repair-deficient mutant mei-9a suggests the possibility that (a) the excision-repair-pathway may not function in misrepair and (b) the undefined misrepair pathway may be dominant pathway for postreplication repair in Drosophila since mei-9a females presumably have functional postreplication repair and misrepair capacity. The suggestion that the CAS postreplication-repair pathway and the excision-repair pathway function primarily in repair, and an undefined pathway in misrepair is in line with the finding that with mus104D1, no significant increase was found in spontaneous complete loss, but with mus101D1, mus302D1, mei-41D5 and mei-9a significant increases were observed. Results on induced complete loss, with the exception of those with mei-41D5, show a poor correlation with other classes of loss of each of the mutants. Possible explanations for this discrepancy are discussed.

Animals↗
PubMed1980

Evidence that the repair deficient mei-9a female in Drosophila melanogaster is a strong potentiator of chromosome loss induced in the paternal genome by dimethylnitrosamine.

From mating of Xc2/BsYy+ males treated or not with 2.5 mM DMN (dimethylnitrosamine) with repair-deficient mei-9a females or with ordinary females, induced frequencies of observed (recovered) chromosome loss were 3.69% and 0.65% and inferred (non-recovered) ring-X loss based on shifts in sex ratio (male male/female female) was 47.9% and 9.4%, respectively. Results indicate that the mei-9a female is a strong potentiator of DMN-induced chromosome damage in sperm and suggest that DMN-induced chromosome lesions are produced in substantially higher frequency in treated sperm than deducible after crosses with repair-efficient females.

Animals↗
PubMed1980

Comparison of SCH-12679 and thioridazine in aggressive mental retardates.

SCH-12679, a benzazepine derivative, was compared to thioridazine and to placebo on the aggressive behaviour of mentally retarded patients. After a three-week chlorpromazine (100 mg t.i.d.) standardizaton period, no significant differences between the three treatment groups were observed in their abnormal behaviour. During the comparative phase, patients treated with SCH-12679 became less hyperative and less agitated while those treated with thioridazine became more violent, more choleric and more provocative. The clinical investigator and the nursing staff found significant differences between the active drugs. As compared to the placebo, SCH-12679 improved the behaviour of the patients while thioridazine aggravated their condition. No important adverse reaction was found and the drugs did not interact with the sex of the patients and the presence of epilepsy. The results suggest that, in mental retardation, physical restraint of hyperactivity might induce aggressivity and that one should be cautious in using neuroleptics in nonpsychotic patients.

Aggression↗
PubMed1979

Gas-liquid chromatographic method for the measurement of plasma levels of d-7,8-dimethoxy-3-methyl-phenyl-2,3,4,5-tetrahydro-1h-3-benzazepine acid maleate (SCH-12679) and its major metabolites in aggressive mental retardites.

A sensitive gas-liquid chromatographic technique for the quantitative analysis of SCH-12679 (d-7,8-dimethoxy-3-methyl-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine acid maleate) and its major metabolites in plasma of aggressive mental retardates receiving therapeutic doses of the medicament has been developed. The lower limits of detection are 20 ng/ml for SCH-12679, 0.5 ng/ml for 3-desmethyl SCH-12679 and 0.4 ng/ml for 7-desmethyl plus 8-desmethyl SCH-12679. SCH-12679 is estimated with a flame ionization detector. Its metabolites are quantitated using an electron-capture detector after conversion of the compounds to their heptafluorobutyryl derivatives by reaction with the appropriate anhydride. Data on plasma levels of unchanged SCH-12679, 3-desmethyl SCH-12679 and a combination of 7-desmethyl and 8-desmethyl SCH-12679 in fifteen patients treated with the medicament are presented.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1979

Metabolic interaction between amitriptyline and perphenazine in psychiatric patients.

1. Steady-state plasma level samples of sixty-five schizophrenic patients from two psychiatric hospitals assigned to three treatment groups (amitriptyline 150 mg/day, perphenazine 20 mg/day and a combination of amitriptyline and perphenazine at 150 mg and 20 mg/day) were assayed for amitriptyline (AT), endogenous nortriptyline (NT) and perphenazine (PPZ) using gas-liquid chromatography. 2. Results reveal that AT and NT levels are independent of sex and hospital environment. 3. PPZ significantly increased the steady-state NT plasma levels, probably through inhibition of the hydroxylation biotransformation pathway, but had no effect on AT levels, thus indicating that PPZ has no influence on the desmethylation pathway, or alternatively, the hydroxylation of AT.

Adult↗