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Biomedical subjects

A R Jones

Publications and source records attributed to A R Jones.

At least 109 records · Page 6Linked to original sources
PubMed1985

The anti-glycolytic action of (S)-alpha-chlorohydrin on epididymal bovine spermatozoa in vitro.

(S)-alpha-Chlorohydrin interferes with glycolysis in bovine spermatozoa whereas the (R)-isomer is ineffective. The action of the (S)-isomer, which involves inhibition of the reaction catalysed by glyceraldehyde 3-phosphate dehydrogenase, is not immediate but is evident only after a brief period of incubation with the spermatozoa. This inhibitory action is prevented when glycerol is present suggesting that the mechanism of action of (S)-alpha-chlorohydrin requires its oxidation to (S)-3-chlorolactaldehyde which is the active metabolite. Addition of racemic 3-chlorolactaldehyde to bovine spermatozoa caused immediate inhibition of glycolysis. It is proposed that the action of (S)-alpha-chlorohydrin in bovine spermatozoa is similar to that observed in the spermatozoa of other species in being a two-stage process; first, its oxidation to (S)-3-chlorolactaldehyde, and then inhibition of the glycolytic enzyme by this metabolite.

Aldehydes↗
PubMed1985

Production of (S)-3-chlorolactaldehyde from (S)-alpha-chlorohydrin by boar spermatozoa and the inhibition of glyceraldehyde 3-phosphate dehydrogenase in vitro.

The (S)-isomer of the male antifertility agent alpha-chlorohydrin was metabolized by mature boar spermatozoa in vitro to (S)-3-chlorolactaldehyde. This oxidative process, which did not occur when (R)-alpha-chlorohydrin was offered as a substrate, was catalysed by an NADP+-dependent dehydrogenase that converts glycerol to glyceraldehyde. (S)-3-chlorolactaldehyde, produced by this metabolic reaction or when added to suspensions of boar spermatozoa, was a specific inhibitor of glyceraldehyde 3-phosphate dehydrogenase as assessed by the accumulation of fructose 1,6-bisphosphate and the triosephosphates. When glycerol and (S)-alpha-chlorohydrin were added concomitantly to boar spermatozoa in vitro, the presence of glycerol decreased the degree of inhibition of glyceraldehyde 3-phosphate dehydrogenase. Extracts of glyceraldehyde 3-phosphate dehydrogenase that were obtained from boar spermatozoa incubated with (S)-alpha-chlorohydrin or (R,S)-3-chlorolactaldehyde showed significant reductions in their enzymic activity.

Aldehydes↗
PubMed1984

The action of (S)-alpha-chlorohydrin and 6-chloro-6-deoxyglucose on the metabolism of guinea pig spermatozoa.

(S)-alpha-Chlorohydrin inhibits the conversion of fructose to lactate by mature guinea pig spermatozoa in vitro. At a concentration of 2mM, there is a specific inhibition of glyceraldehyde-phosphate dehydrogenase resulting in the accumulation of fructose-1,6-bisphosphate, dihydroxyacetone phosphate and glyceraldehyde-3-phosphate and a concomitant decrease in the concentration of endogenous lactate. (R,S)-[3-36Cl]-alpha-Chlorohydrin is metabolised by the spermatozoa to 3-chlorolactaldehyde of unknown configuration. Exogenous (R,S)-3-chlorolactaldehyde (2mM) is an inhibitor of glyceraldehyde-phosphate dehydrogenase in guinea pig spermatozoa, whereas (R)-alpha-chlorohydrin (10mM) has no significant effect on the metabolism of fructose. 6-Chloro-6-deoxyglucose (10mM) inhibits glyceraldehyde-phosphate dehydrogenase in guinea pig spermatozoa in vitro and is metabolised to 3-chlorolactaldehyde which is presumably the (S)-isomer. The anti-glycolytic actions of (S)-alpha-chlorohydrin and 6-chloro-6-deoxyglucose in guinea pig spermatozoa are suggested to be due to the action of a common metabolite, (S)-3-chlorolactaldehyde.

Animals↗
PubMed1984

Protocol for evaluation of automated blood cell counters. International Committee for Standardization in Haematology (ICSH).

This protocol is proposed for the evaluation of automated blood cell counters to assess the performance, advantages and limitations of such instruments. It is based on the International Committee for Standardization in Haematology (ICSH) 'Protocol for type testing equipment and apparatus used for haematological analysis' (1978a) and the British Committee for Standardization in Haematology 'Guidelines for the evaluation of instruments used in haematology' (Shinton, England & Kennedy, 1982). The document has been prepared by the ICSH Panel on Cytometry after discussion with colleagues. This tentative protocol will be reviewed 1 year after publication, in accordance with the ICSH rules, before it is adopted as a definitive standard.

Blood Cell Count↗
PubMed1984

The action of (R)- and (S)-alpha-chlorohydrin and their metabolites on the metabolism of boar sperm.

The action of (R,S)-alpha-chlorohydrin in inhibiting glycolysis in boar sperm is due to the (S)-isomer. Its effect on the concentrations of glycolytic intermediates suggests that the pathway is inhibited at the glyceraldehyde 3-phosphate dehydrogenase reaction. alpha-Chlorohydrin is oxidized by boar liver homogenates via 3-chlorolactaldehyde to 3-chlorolactate. Racemic mixtures of both compounds, and a proposed metabolite, 3-chloropyruvate, inhibit the oxidative metabolism of fructose, lactate and pyruvate possibly by interfering with processes occurring within the sperm mitochondria. It is proposed that the toxic action of these metabolites account for the effects of (R)-alpha-chlorohydrin on sperm motility, as this compound possesses no antifertility activity of itself.

Animals↗
PubMed1984

Occurrence of mammary tumors in rats after exposure to tritium beta rays and 200-kVp X rays.

The RBE for tritium was estimated in reference to 200-kVp X rays, using acceleration of breast tumor appearance in the female Sprague-Dawley rat as the end-point. Chronic X-ray doses of 0.3-2.0 Gy were delivered over 10 days. Intraperitoneal injections of tritiated water ranging in concentrations from 45 to 370 MBq/100 g body wt were administered, followed by four additional injections at 2-day intervals and half of the initial concentrations. Seventy-five percent of the total tritium dose was delivered to the mammary gland within the first 10 days and 95% within the first 20 days after the start of the tritium exposure. RBE estimations were based on various criteria including the tumor incidence per Gy at 450 days postirradiation and the time required to induce tumors in 50% of the animals at risk. The results suggest that tritium beta rays are about 1.1-1.3 times more effective than chronic 200-kVp X rays for acceleration of the appearance of rat mammary tumors. However, the uncertainties involved in these calculations are such that the effects of tritium beta rays could not be reliably distinguished from those of chronic 200-kVp X rays. Measured differences in RBE values were slightly larger for the comparison between acute and chronic X rays than for the comparison between chronic tritium beta rays and chronic X rays.

Animals↗
PubMed1983

Formation of the active antifertility metabolite of (S)-alpha-chlorohydrin in boar sperm.

The male antifertility agent (S)-alpha-chlorohydrin (I) is metabolized by boar sperm to (S)-3-chlorolactaldehyde (II) by an enzyme that is involved in the oxidation of glycerol to glyceraldehyde. The presence of glycerol decreases the activity of this enzyme towards (S)-alpha-chlorohydrin in vitro thereby preventing the formation of (S)-3-chlorolactaldehyde, an inhibitor of glyceraldehyde 3-phosphate dehydrogenase in boar sperm.

Animals↗
PubMed1983

The effect of alpha-chlorohydrin on the oxidation of fructose by rabbit spermatozoa in vitro.

(R,S)-alpha-Chlorohydrin inhibits the oxidative metabolism of fructose in mature rabbit spermatozoa in vitro. This effect is not noticeable at concentrations of the compound up to 10 mM, is evident at 50 mM but at 100 mM is apparently accompanied by cell damage. At a concentration of 50 mM, (R,S)-alpha-chlorohydrin causes the specific inhibition of the enzyme glyceraldehyde 3-phosphate dehydrogenase and is metabolised by the spermatozoa to 3-chlorolactaldehyde of unknown configuration. Exogenous (R,S)-3-chlorolactaldehyde (5 mM and 10 mM) appears to inhibit glyceraldehyde 3-phosphate dehydrogenase in rabbit spermatozoa as well as affecting other metabolic pathways. The ineffectiveness of (R,S)-alpha-chlorohydrin as an anti-fertility agent in male rabbits may be due to the inability of the spermatozoa to produce a sufficient amount of the inhibitory metabolite (S)-3-chlorolactaldehyde.

Animals↗
PubMed1983

Antifertility actions of alpha-chlorohydrin in the male.

Non-steroidal chemicals that affect male fertility have been known for over 25 years but only one compound, alpha-chlorohydrin, possesses most of the attributes of an ideal male contraceptive. In the male rat, for example, continuous daily oral administration of low doses produces an almost immediate and continuous antifertility response that ceases when treatment is withdrawn. Such a dose regime does not interfere with libido, is apparently not toxic and the action is specific towards mature sperm. Furthermore, the action of the compound is species-specific: it is effective in the rat, ram, boar, guinea pig, hamster, rhesus monkey and upon ejaculated human sperm but it is ineffective in the mouse and the rabbit. High doses of alpha-chlorohydrin can be neurotoxic, nephrotoxic and, in rats, lead to prolonged or permanent infertility. However, the antifertility response and the toxicity of racemic alpha-chlorohydrin may be due, respectively, to the separate enantiomers. No other antifertility chemical has been investigated to such an extent as alpha-chlorohydrin; this article reviews the progress that has been achieved with alpha-chlorohydrin during the past six years.

Animals↗
PubMed1983

The fate of N-methyl-N'-(hydroxymethyl)thiourea in the rat.

1. The fate of N-methyl-N'-(hydroxy[14C]methyl)thiourea (MHT) has been studied in the male Sprague-Dawley rat. The compound is degraded to N-methylthiourea and formaldehyde. 2. N-Methylthiourea is excreted as a urinary metabolite whereas the formaldehyde is not excreted, either in the urine or the expired air, but is metabolized via formate to CO2. 3. At least 50% of an i.p. dose (100 mg/kg) of MHT is excreted unchanged and some of this undergoes hydrolysis within the urine to N-methylthiourea and formaldehyde. Production of formaldehyde leads to the formation of the urinary artefact N-(hydroxymethyl)urea. 4. Tissue-distribution studies with 14C-MHT have shown that radioactivity is selectively associated with the thyroid gland. A preliminary investigation has indicated that MHT has anti-thyroid hormone activity as it lowers the thyroxine in rat serum.

Animals↗
PubMed1982

The effect of the isomers of alpha-cholorohydrin and racemic beta-chlorolactate on the rat kidney.

The (R)- and (S)-isomers of the male antifertility agent alpha-chlorohydrin have been synthesized. When administered to rats, the (R)-isomer induced a period of diuresis and glucosuria, whereas the (S)-isomer, which possesses the antifertility activity, had no detrimental action on the kidney. Neither of the isomers of alpha-chlorohydrin nor those of an active analogue, 3-amino-1-chloropropan-2-ol, had any inhibitory activity on the oxidative metabolism of glucose or lactate in isolated kidney tubules. However, beta-chlorolactate, a metabolite common to both compounds, inhibited the oxidation of glucose, lactate, pyruvate and glutamate to CO2. It is proposed that the antifertility action of the (S)-isomers of alpha-chlorohydrin and 3-amino-1-chloropropan-2-ol is unrelated to the renal toxicity of the (R)-isomers, a toxic action involving the inhibition of oxidative metabolism by (S)-beta-chlorolactate or a further product of this metabolite.

Animals↗
PubMed1982

Inhibition of fructolysis in boar spermatozoa by the male antifertility agent (S)-alpha-chlorohydrin.

The (S)-isomer of the male antifertility agent alpha-chlorohydrin strongly inhibited the oxidative metabolism of fructose by boar spermatozoa in vitro. The result of this action, which has been deduced to be an inhibition of glyceraldehydephosphate dehydrogenase, caused an accumulation of fructose-1,6-bisphosphate and the triosephosphates, and a decrease in substrate-level phosphorylation with a concomitant lowering of the energy charge potential of the spermatozoa. The (R)-isomer of alpha-chlorohydrin had no inhibitory activity on fructolysis. A study of the comparative metabolism of (R)-[3-36Cl]-alpha-chlorohydrin and (R,S)-[3-36Cl]-alpha-chlorohydrin by boar spermatozoa showed that it is the (S)-isomer that specifically undergoes a process of oxidative metabolism to (R)-3-chlorolactaldehyde. It is proposed that this endogenous oxidation product, which has the same absolute configuration as the substrate for glyceraldehyde-phosphate dehydrogenase, is the active metabolite of (S)-alpha-chlorohydrin that inhibits this enzyme. Exogenous (R,S)-3-chlorolactaldehyde inhibited the oxidative metabolism of fructose by boar spermatozoa, apparently by a mechanism similar to that of (S)-alpha-chlorohydrin.

Adenine Nucleotides↗
PubMed1982

Formaldehyde metabolism by the rat: a re-appraisal.

1. The metabolism of [14C]formaldehyde has been investigated in the male Sprague-Dawley rat. It is extensively oxidized to CO2 and formate, which is excreted in the urine. 2. Two radioactive compounds isolated from the urine of rats dosed with [14C]formaldehyde have been identified as N-hydroxymethylurea and N,N'-bis-(hydroxymethyl)urea, and shown to be urinary artefacts. 3. Previous studies of the metabolism of formaldehyde by rats have been re-appraised. Differences in the rate of oxidation of formaldehyde in various strains of rats result in the excretion of different urinary metabolites and, in some cases, formaldehyde. Excretion of formaldehyde leads to the formation of several artefacts depending on the components present in the urine.

Animals↗
PubMed1982

Some observations on the urinary excretion of glycine conjugates by laboratory animals.

1. An isotope dilution assay has been developed for measuring the amount of conjugated glycine present in urine. The average daily excretion of conjugated glycine by male and female mouse, rat, guinea-pig and rabbit has been determined. 2. The glycine conjugates excreted by the four species have been identified. All species excreted only benzoylglycine and phenylacetylglycine. 3. The metabolism of [carboxy-14C]benzoic acid and [1-14C]phenylacetic acid has been investigated in the Sprague-Dawley rat. When administered over a range of concn. from 10 microgram/kg to 1g/kg, benzoic acid is converted to hippuric acid while phenylacetic acid is converted to phenylacetylglycine and phenylacetylglutamine. 4. Neither the rate of excretion nor the composition of the urinary metabolites arising from each acid is changed when low doses of one acid are co-administered with a high dose of the other. 5. The origin of the conjugated benzoic and phenylacetic acids is discussed.

Animals↗