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Biomedical subjects

A R Jones

Publications and source records attributed to A R Jones.

At least 145 records · Page 8Linked to original sources

The antifertility action of alpha-chlorohydrin: enzyme inhibition by alpha-chlorohydrin phosphate.

Preparations of the enzymes glyceraldehyde-3-phosphate dehydrogenase and triosephosphate isomerase are shown to be inhibited by alpha-chlorohydrin phosphate (II) in a competitive and non-competitive manner, respectively. alpha-Chlorohydrin (I), glycidol and epi-chlorohydrin have no inhibitory activities suggesting that their antifertility actions are due to their metabolism in vivo to alpha-chlorohydrin phosphate.

Animals↗

The oxidative metabolism of alpha-chlorohydrin in the male rat and the formation of spermatocoeles.

1. The oxidative metabolism of [3-36C]chloropropan-1,2-diol (alpha-chlorohydrin, I) was studied in male rats. Two metabolites were isolated and identified as beta-chlorolactic acid (IV) and oxalic acid (V). 2. Neither alpha-chlorohydrin nor beta-chlorolactate was concentrated in any tissue. Traces of an intermediate metabolite, beta-chlorolactaldehyde (III) were detected in the urine within 4 h of administration. Studies in vitro indicated that the metabolic pathway is: alpha-chlorohydrin leads to beta-chlorolactaldehyde leads to beta-chlorolactic acid. 3. A comparative study of the metabolism of 36Cl- and 14C-beta-chlorolactate showed that oxalate was produced slowly and, as calcium oxalate, caused a type of renal glomerular nephritis. This pathological condition is responsible for the diuretic action of both alpha-chlorohydrin and beta-chlorolactate and, in higher doses, for their toxicities. 4. The role of oxalate, as a metabolite of alpha-chlorohydrin and of a number of related compounds, in inducing the formation of spermatocoeles in the male rat reproductive tract is discussed.

Animals↗

Alkylating esters. X. The reaction of some aziridine alkylating agents with methionine and S-methyl cysteine.

Two biologically active aziridine ring-containing compounds, N,N-ethylene urethane (I) and N,N-ethylene urea (II), have been shown to react with methionine in dilute phosphate buffer (pH 7.4) at 37 degree C. Degradative procedures indicate that the aziridine ring effectively alylates the thio ether group of methionine and other thio ether-containing amino acids to produce sulphonium salts (V). By using [35S]methionine, the sulphonium salts have been shown to be quite stable under physiological conditions (t1/2 7--9 days) hydrolysing to convert the methionine residue to homoserine. It is proposed that similar alkylations of methionyl residues in vivo by aziridine-alkylating agents may explain the complex, and al yet unknwn, metabolic fate of the aziridine ring and could also be a factor contributing to the diverse effects that these agents have on living cells.

Alkylating Agents↗

The oxidative metabolism of alpha-chlorohydrin and the chemical induction of spermatocoeles.

alpha-Chlorohydrin (I) is oxidatively metabolized to beta-chlorolactic acid (III) and oxalic acid (IV). Deposition of calcium oxalate within the renal tubules is responsible for the toxic effects of alpha-chlorohydrin and a similar action on the epididymis or epididymal blood vessels could initiate the formation of spermatocoeles from this and other male antifertility agents.

Animals↗

Transformation of lymphocytes from patients awaiting cadaver renal transplants.

The response of lymphocytes from prospective kidney transplant recipients to inactivated donor lymphocytes (one-way mixed-lymphocyte reaction (M.L.R.)) and to phytohaemagglutinin (P.H.A. response) was measured before transplantation of cadaver kidney allografts in 78 and 75 cases respectively. M.L.R. results from patients whose grafts had failed within 3 or 6 months compared with M.L.R. results from patients whose grafts continued to function at the same times showed only slight differences irrespective of whether the data was expressed as a relative response or a mitotic index. Because of the large overlap in values, it was concluded that the M.L.R. test was of limited value in predicting graft prognosis. Pretransplantation P.H.A. responses from patients whose grafts failed within 3 or 6 months were significantly different from those shown by patients whose grafts remained functioning at those times. It is suggested that lymphocyte responsiveness to P.H.A. before transplantation may be of value in predicting the fate of renal allografts.

Adolescent↗

A statistical technique for determining compliance with dual hygienic standards.

A mathematical technique was developed to calculate log-normal distribution for sample results. This is then compared with a Limiting distribution defined by the sampling time, the Time-Weighted Average and the Ceiling Limit standard for the material tested. The technique provides a more effective means to decide if either or both the T.W.A. or Ceiling Limit has been exceeded. Sample times from 10 minutes to 4 hours are considered. A similar technique has previously been reported for evaluating benzene exposures. Examples are provided to illustrate the procedure.

Environmental Pollutants↗

The entry of alpha-chlorohydrin into body fluids of male rats and its effect upon the incorporation of glycerol into lipids.

The rate of entry of alpha-chlorohydrin into rat rete testis fluid has been studied using the 14-C and 36-Cl-labelled compounds. The alpha-chlorohydrin crosses the blood-testis barrier and the concentration of radioactivity in rete testis fluid attained blood levels within 45 min. Within 3 hr of a single injection of [14-C] alpha-chlorohydrin, radioactivity was widely distributed in body fluids, and was present in the lipids of the brain, testis, epididymis and epididymal fat pads. No radioactivity was found in tissue lipids following the administration of [36-Cl] alpha-chlorohydrin, which suggests that dechlorination of this compound occurs before its incorporation. Neither a single high dose nor repeated low doses of alpha-chlorohydrin induced changes in the incorporation of [14-C] glycerol into lipids of the brain, testis, epididymis and epididymal fat pads.

Animals↗

The metabolism of 3-chloro,- 3-bromo- and 3-iodoprpan-1,2-diol in rats and mice.

1. The metabolism of the 3-halopropan-1,2-diols (alpha-halohydrins) has been investigated in rats and mice. Apart from 3-chloropropan-1,2-diol (I), of which some 10% is excreted unchanged by both species, the compounds are completely degraded following intraperitoneal administration. 2. The alpha-halohydrins are detoxicated by conjugation with glutathione and produce two urinary metabolites, isolated and identified as S-(2,3-dihydroxypropyl)cysteine (VII) and the corresponding mercapturic acid N-acetyl-S-(2,3-dihydroxypropyl)cysteine (VIII). 3. When incubated with rat liver supernatant, the compounds do not conjugate with glutathione and their general chemical reactivity suggests that they react via a common intermediate proposed to be glycidol (2,3-epoxypropanol, IV). As the epoxide produces the same urinary metabolites as the alpha-halo-hydrins, and conjugates with glutathione either with or without liver supernatant to form the primary metabolite S-(2,3-dihydroxypropyl)glutathione (VI), glycidol is also proposed to be the reactive intermediate in vivo. 4. The role of epoxides in intermediary metabolism is discussed.

1-Propanol↗