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.
(R,S)‐Ornidazole, an effective antifertility agent for male rats at 400 mg/kg/day, was ineffective at this dose in male mice and at 1000 mg/kg/day caused neural effects. The compound was not excreted unchanged and more polar metabolites and Cl – were detected in 0–8 h urine following a single injection (400 mg/kg). In 8–24 h urine even these metabolites and most Cl ion were absent, indicating rapid metabolism of ornidazole. There was no organ specific accumulation of 36 Cl‐(R,S)‐ornidazole in murine tissues. After injection of 36 Cl‐(R,S)‐α ‐ chlorohydrin, another antifertility agent in the rat but not the mouse, there was also no tissue‐specific accumulation of radioactivity in the reproductive tract of either species. Urinary excretion rates of α‐chlorohydrin were twice as rapid in mice as in rats. In mice, α‐chlorohydrin was the major urinary metabolite, but in the rat metabolites included Cl – , 3‐chlorolactate (BCLA) at 5 and 10 h and BCLA only at 24 h. BCLA was the major metabolite detected in most tissues at 10 and 24 h. In the rat cauda (but not caput) epididymidis the glycolytic inhibitor 3‐chlorolactaldehyde was present at 5 h (but not 10 h), indicative of early metabolism. These results demonstrate a greater metabolism and excretion of putative antifertility agents in the mouse than the rat, lowering the amount of effective inhibitor circulating in the animal, which may explain why (R,S)‐α‐chlorohydrin and (R,S)‐ornidazole are ineffective in this species at the dosages and injection times used, despite their spermatozoa being sensitive to inhibition by (R,S)‐α‐chlorohydrin in vitro.
Abstract1. 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.
1. The metabolism of 2-bromo[U-14C]ethanol and [U-14C]ethylene oxide has been studied in the rat.2. As both compounds give rise to similar amounts of two urinary metabolites, identified as S-(2-hydroxyethyl)cysteine and N-acetyl-S-(2-hydroxyethyl)cysteine, it is proposed that 2-bromoethanol is converted into ethylene oxide in vivo.3. A minor metabolite of 2-bromoethanol has been identified as N-acetyl-S-(carboxymethyl)cysteine.4. The metabolism of bromoacetaldehyde and bromoacetic acid has been investigated; N-acetyl-S-(carboxymethyl)cysteine has been shown to be a common urinary metabolite.5. An oxidative metabolic pathway is proposed for 2-bromoethanol, via bromoacetaldehyde and bromoacetic acid, to N-acetyl-S-(carboxymethyl)cysteine.
An investigation has been carried out into the possibility of using polarization methods to characterize clouds of irregular particles. Measurements were made at scattering angles between approximately 115° and 135°, where it was expected that polarization effects would have maximum variation with shape. It was found that the angular variation of any polarization property was similar for most particles. Further, as a consequence of reciprocity, the useful parameters were limited to the scattered intensities for two incident polarization states and one cross-polarized intensity. The only useful correlation appeared to be between cross-polarization and the `roundness' of the particles, although different correlations are observed between particles which are inherently isotropic and those which are anisotropic. The main conclusion of the study is that polarization can be used to measure the average roundness of particles in a cloud and has the potential to discriminate between crystals of different structure.
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