Determination of homocysteine in urine.
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Biomedical subjects
Publications and source records attributed to M H Briggs.
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Reversed-phase high-performance liquid chromatography with UV detection is studied for the determination of both progestogenic and oestrogenic components of oral contraceptive formulations. The applicability of the assay is demonstrated for a number of different progestogen-oestrogen combinations in both conventional tablet and novel "paper" formulations. The results show that the method developed is a versatile technique for the routine assay of these pharmaceutical formulations.
We tested 64 perfumes and aftershaves for mutagenicity in Salmonella typhimurium strains TA98 and TA100; most were tested both with and without metabolic activation. None of the test compounds gave a positive mutagenic response. The available amounts of some test samples were very small, however, and the possibility that larger samples might have produced positive results cannot be altogether discounted. Some tests indicated the presence of cytotoxic substances which require chemical analysis.
The present work involved the administration of both ethynyl estradiol and levonorgestrel to groups of rats, followed by determination of the homocysteine excretion rate in urine. The results indicate that a statistically significant difference exists between the excreted levels of homocysteine in the urine of both control and levonorgestrel-treated rats and the levels shown by rats treated with ethynyl estradiol. The implications of these results are discussed, especially with respect to observations which indicate that homocysteine may be a precipitating factor in the development of thrombosis. Also included in this paper is a study which confirms the identity of the HPLC peak as being homocysteine by forming a radioactive derivative of this particular sulphydryl-containing amino acid, and then analysing the resulting mixture by TLC.
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Plasma vitamin A and retinol-binding protein (RBP) concentrations have been studied in women using oral contraceptives (OC) for up to 4 years. In eight women taking an oestrogenic OC(1 mg of norethisterone acetate + 50 micrograms of ethinyloestradiol) values almost doubled within 6 months, but diminished somewhat after 4 years. Saturation of RBP with retinol remained fairly constant. Five lactating women who took progestogen-only OC (30 micrograms of levonorgestrel or 350 micrograms of norethisterone) showed no significant alteration in plasma vitamin A or RBP concentrations as compared with nine lactating non-OC users. All lactating women showed significant differences between the highest and lowest plasma vitamin A (P less than 0.005) and RBP (P less than 0.05) concentrations during the first 6 months of lactation. Highest values occurred 11-12 weeks postpartum and the lowest at 15-17 weeks. Percentage saturation of RBP with retinol was significantly higher (P less than 0.005) when vitamin A concentration was highest.
Groups of 10 pregnant albino rats received a single subcutaneous injection of oil containing synthetic sex hormones on day 13 of pregnancy. Control rats received only oil. The steroid doses were ten times those used as oral hormonal pregnancy tests for humans. Norethisterone acetate (NEA) was given at 2 mg/kg, ethynylestradiol (EE) at 4 micrograms/kg, and NEA + EE together at these same doses. The concentration of penile total specific androgen-receptor binding sites in cytosol preparations was measured by means of in vitro uptake of tritiated methyltrienolone (3H-R 1881). No significant difference was observed between controls and treated groups for androgen-receptor concentrations in preparations from male offspring at birth, or in others reared to day 30. Rat penile androgen receptors showed high affinity for 5 alpha-dihydrotestosterone. Testosterone showed weaker binding (ca. 10%), while R 1881 showed much greater affinity (ca. 550%). Very weak binding was shown by progesterone, estradiol 17 beta, and the synthetic steroids investigated in this study.
Healthy, nonsmoking, normotensive, well-motivated young women were assigned at random to one of four different commercial, low-estrogen oral contraceptives. Measurements of biochemical parameters were made on two blood specimens collected from fasting subjects late in the pretreatment cycle, then again late in each treatment cycle for 12 months. All the women assigned to one product (0.5 mg norethindrone + 35 micrograms ethinyl estradiol) dropped out of the study before the end of the fifth cycle, but discontinuations with the other three products were few. Though the numbers of subjects were small, the groups were closely matched, and most of the metabolic differences were statistically significant. Products containing ethynodiol diacetate and norethindrone were associated with increases in serum total cholesterol and triglycerides but decreases in high-density-lipoprotein-cholesterol. In contrast, the levonorgestrel-containing preparation produced significantly less of an effect on these tests. A similar pattern was seen with a range of blood coagulation and fibrinolytic factors. Minimal alterations were seen with the levonorgestrel preparation, whereas those containing norethindrone or ethynodiol diacetate showed marked increases in factors I, VII, VIII and X and plasminogen, associated with a decrease in antithrombin III. Differences in the metabolic impact of the various commercially available low-estrogen preparations, combined with their effects on intermenstrual bleeding, allow a choice of the progestogen component most suitable for general use.
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Presented is a study, using multielement neutron activation analysis, of the elemental composition of blood plasma and milk in a group of lactating Australian women. Having established baseline values for nine elements, the authors studied factors affecting concentrations in milk and the partitioning of those elements between plasma and milk. Changes in this partitioning with the progression of lactation were demonstrated, and their nutritional implications for the exclusively breast-fed baby discussed. Progestogen-only oral contraceptives had no significant effect on levels of any of the trace elements in either blood or milk.
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Treatment of pregnant rats from days 13 through 19 with a synthetic steroid known to inhibit 3 beta-hydroxysteroid oxidoreductase was associated with a significant reduction in the capacity of fetal Wolffian ducts to metabolize dehydroepiandrosterone. In contrast, similar treatment with norethisterone acetate, alone or in combination with ethynylestradiol, or medroxyprogesterone acetate, at up to 100 times the human dose, was without effect on metabolism of dehydroepiandrosterone. It is suggested that the use of synthetic progestogens during pregnancy is unlikely to increase the risk of hypospadias due to inhibition of testosterone biosynthesis.
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