Amoxycillin and clavulanic acid in intra-abdominal and pelvic sepsis.
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Administration, Oral↗
Biomedical subjects
P Ball
Publications and source records attributed to P Ball.
Interactions of catecholestrogens with cytoplasmic and nuclear estrogen receptors in rat pituitary gland and hypothalamus.
The affinity of a series of catecholestrogens for 7S cytoplasmic receptor proteins from hypothalamus and pituitary gland of ovariectomised rats was assessed in vitro by a competitive charcoal binding assay at 4 degrees C. The equilibrium dissociation constants (Ki) of catecholestrogens 4-hydroxyestradiol, 4-hydroxyethynylestradiol, 2-hydroxyestradiol, 2-hydroxyethynylestradiol, and 4-hydroxyestrone were of the same order (Ki: 0.3-0.6 nM) as those of estradiol and ethnylestradiol (Ki: 0.1 nM). Methylation of 2-hydroxyestradiol led to a substantial loss of binding affinity. Tritium-labelled receptor complexes were demonstrated in KCl extracts of purified nuclei from pituitary and hypothalamic tissue 1 h after intravenous injection of 0.1 mCi tritiated 2- or 4-hydroxyestradiol. These macromolecular complexes sedimented in the 5-6S region of 5-20% (w/v) sucrose gradients containing 0.4 M-KCl. Further evidence for the translocation of estrogen receptors by catecholestrogens into the nuclei of rat pituitary and hypothalamus was the increase in nuclear receptor concentrations, measured by exchange assay, 1 h after the intraperitoneal injection of 0.1 mg unlabelled catecholestrogen. Administration of 4-hydroxyestradiol and 4-hydroxyethynylestradiol increased nuclear receptor concentrations to the same maximal levels as those following application of the same dose of estradiol or ethynylestradiol, whereas the respective 2-hydroxylated compounds exhibited only 60-70% of the maximal translocating capacity. The in vivo translocating capacities of the various catecholestrogens tested at this dose correlated well with their binding affinities for cytosol receptors determined in vitro.
Animals↗
Tetracycline resistance genes from Bacillus plasmid pAB124 confer decreased accumulation of the antibiotic in Bacillus subtilis but not in Escherichia coli.
Expression of tetracycline resistance by genes originating in the Bacillus plasmid pAB124 was examined in both Bacillus subtilis and Escherichia coli host cells. Expression of resistance in B. subtilis by genes from pAB124 was inducible and associated with decreased accumulation of the antibiotic. A fragment of pAB124 carrying the genes coding for tetracycline resistance was cloned into the E. coli plasmid RSF2124. The cloned fragment conferred a low level of resistance in E. coli, but this was not associated with decreased uptake of tetracycline and was not inducible.
Bacillus subtilis↗
Catecholestrogens and induction of sexual behavior in the ovariectomized rat.
The ability of the catecholestrogens, 4-hydroxyestradiol (4-OHE2) and 2-hydroxyestradiol (2-OHE2) to induce lordosis in ovariectomized rats primed with progesterone was assessed following either short- or long-term exposure to the steroids. 4-OHE2 successfully induced lordosis whether administered as two bolus intrajugular injections separated by a 3-hour interval or continuously for 7 days via subcutaneously implanted osmotic minipumps. 2-OHE2, however, was ineffective under both conditions. When administered subcutaneously in conjunction with 3 days of estradiol benzoate (E2B) treatment, neither of the catecholestrogens exhibited any antiestrogenic effect as compared with the lordosis response to E2B alone. Likewise, simultaneous administration of 2-OHE2 did not significantly alter the response to intrajugular injections of estradiol (E2) or 4-OHE2. The results indicate that 4-OHE2 (but not 2-OHE2) mimicks the lordosis-inducing action of E2 and that neither catecholestrogen has any antiestrogenic effect in this behavioral test system.
Animals↗
Effects of catecholestrogens on luteinizing hormone levels in long tem ovariectomized adult rats.
The long term ovariectomized adult rat was used to test the effects of exogenous estradiol, 4-hydroxyestradiol, and 2-hydroxyestradiol on LH secretion. To this end, different doses of estradiol 3-benzoate, 4-hydroxyestradiol 3,4-dibenzoate, and 2-hydroxyestradiol 2,3-dibenzoate were injected daily at 0800 h, and the LH serum levels were measured on 4 experimental days. At a dose of 1 micrograms/day, estradiol benzoate lowered LH secretion, beginning 48 h after the first injection (morning of day 2), and induced a characteristic LH surge 10 h later. 4-Hydroxyestradiol dibenzoate at the same dose produced less suppression of LH on the morning of day 3, but caused a comparable and highly significant surge on the same evening. Higher doses (3 and 10 micrograms/day) resulted in the same pattern seen with estradiol benzoate. 2-Hydroxyestradiol dibenzoate at comparable doses had no effect. Only extremely high doses (129 micrograms/day) caused slight suppression of tonic LH secretion 72 h after the first injection, and inconsistent LH elevations occurred on the same evening. It is concluded that in this model, catecholestrogens act as estrogens with respect to LH suppression and release, with 4-hydroxyestradiol being a potent estrogen and 2-hydroxyestradiol a weak estrogen.
Animals↗
4-Hydroxyestradiol-17 beta and 4-hydroxyestradiol-17 alpha: comparative studies on central and peripheral effects of two epimeric catecholestrogens.
4-Hydroxyestradiol-17 beta and 4-hydroxyestradiol-17 alpha (5 or 20 microgram/d) were continuously s.c. infused for 3 days into ovariectomized adult rats. The serum levels of either epimer were virtually identical when the same dose was administered. 4-Hydroxyestradiol-17 beta significantly altered body and uterus weight and LH serum levels (negative and positive effects) at both doses tested. 4-Hydroxyestradiol-17 alpha showed no effects even at the 20 microgram/d dose. As both epimers have similar affinities for catechol O-methyltransferase, but their potencies regarding effects on lH serum levels differ markedly, it is concluded that the interaction of catecholestrogens with this enzyme is not essential for their effects on LH release.
Animals↗
Effect of low doses of continuously administered catecholoestrogens on peripheral and central target organs.
Osmotic minipumps containing low doses of either 4-hydroxyoestradiol or 2-hydroxyoestradiol2) were sc implanted for 152 h (6 1/3 day) into immature male and female rats. At the end of the test period the animals were killed and the uterine weight, the vaginal opening, the gonadotrophin serum levels and the gonadal weight monitored. The following results were obtained: 1) a significant increase in the uterine weight and a consistent vaginal opening were observed after 4-hydroxyoestradiol but not after 2-hydroxyoestradiol treatment, 2) LH-levels increased after 2-hydroxyestradiol but not after 4-hydroxyoestradiol; the increase was, however, not significant, 3) FSH-levels and gonadal weights were lowered by 4-hydroxyoestradiol treatment in male animals only; 2-hydroxyoestradiol had not effect on FSH-levels in both sexes, 4) in no instance an antioestrogenic effect of either catecholoestrogen was observed. It is concluded that 4-hydroxyoestrogens - using the above paradigm - have a significant importance on uterine growth and vaginal opening but (on day 6) no role of LH-release, whereas 2-hydroxyoestrogens may increase LH levels (on day 6) but are nearly ineffective with respect to peripheral parameters.
Animals↗
Radioimmunoassay for 4-hydroxyoestrone in human urine.
Under the protection of ascorbic acid a 4-hydroxyoestrone-bovine serum albumin conjugate was prepared containing intact 4-hydroxyoestrone as determined by gas chromatography-mass spectrometry. Using this antigen, antibodies with high affinity and specificity for 4-hydroxyoestrone were raised in rabbits. An assay procedure for the determination of 4-hydroxyoestrone in human urine and the assessment of its reliability are described. The following urinary excretion rates were found: male children 0.29 microgram/24 h, men (less than 50 microgram/24 h, men (20-40 years) 1.6 microgram/24 h, men (less than 50 years) 1.8 microgram/24 h, women, follic, 2.0 microgram/24 h, pre-ov. 5.3 microgram/24 h, luteal 2.4 microgram/24 h, women, pregnant, first trim. 30.0 microgram/24 h, second trim. 64.0 microgram/24 h, third trim. 48.0 microgram/24 h, women, post-men. 1.5 microgram/24 h. Thus the amounts of 4-hydroxyoestrone excreted in human urine are about 1/3 to 1/10 of those of 2-hydroxyoestrone. During the menstrual cycle the excretion rates of 4-hydroxyoestrone are in the same order of magnitude as those of oestradiol and show a clear-cut pre-ovulatory peak.
Adult↗
4-hydroxyestrone, isolation and identification in human urine.
Portions of pregnancy and midcycle urines were submitted to hot acid hydrolysis, extracted with benzene/ethyl acetate and the extracts washed with ascorbic acid buffer. From the remaining organic phase the catecholestrogens were removed with borate buffer and further purified on Sephadex LH-20 columns. After derivatisation 4-hydroxyestrone was separated from the isomeric 2-hydroxyestrone peak were identical with that of authentic 4-hydroxyestrone. After treatment of the extracts with sodium borohydride 4-hydroxyestradiol-17 beta was identified by GC-MS. By the addition of trace amounts of tritiated 4-hydroxyestrone a recovery of 40% was calculated. On the basis of this recovery and the peak heights of the gas chromatograms an excretion of 4 microgram (midcycle) and 40 microgram (pregnancy) of 4-hydroxyestrone/24 h was estimated.
Chromatography, Ion Exchange↗
Effect of catechol oestrogens on induced ovulation in the immature rat.
The 'positive feedback' effect of exogenous oestradiol-17 beta in advancing ovulation induced by pregnant mare serum gonadotrophin (PMSG) has been used in the present study as a model in which to test the possible oestrogenic or antioestrogenic effects of the catechol oestrogens, 2-hydroxyoestradiol (2-OHE2) and 4-OHE2. Sprague-Dawley rats of 26 days of age were injected with 20 i.u. PMSG together with either vehicle alone or test steroids. The animals were killed 72 h later and the Fallopian tubes were examined for the presence of ova. Advancement of induced ovulation by treatment with oestradiol was confirmed; 2-OHE2, in doses of up to 100 micrograms, influenced neither the time of ovulation nor the number of ova present but 4-OHE2 was equipotent with oestradiol in doses varying from 0.5 micrograms (the minimum effective dose for both steroids) to 10 micrograms. The possible antioestrogenic effect of 2-OHE2 was tested by giving a 100 micrograms dose either at the same time or 2 h before PMSG plus 2 micrograms oestradiol or 4-OHE2. The effects of oestradiol and 4-OHE2 were not altered by this treatment. These data show that, in this model of 'positive feedback', 2-OHE2 has neither an oestrogenic nor an antioestrogenic action but that 4-OHE2 has a potent oestrogenic action, thus raising the question of a physiological role for 4-OHE2 in the regulation of ovulation.
Animals↗
Catecholoestrogens (2-and 4-hydroxyoestrogens): chemistry, biogenesis, metabolism, occurrence and physiological significance.
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Adult↗
Radioimmunoassay of 2-hydroxyesterone and 2-methoxyestrone in human urine.
An assay for the quantitative determination of 2-hydroxyestrone and 2-methoxyestrone in human urine is described. The analytical procedure involves several purification steps: XAD-2 column chromatography of urine (1 ml), hot acid hydrolysis under reducing conditions, extraction with benzene/ethyl acetate, separation of monophenolic steroids from catecholestrogens by the formation of borate complexes, and partition between different solvents. Quantitation is achieved by radioimmunoassay using highly specific antibodies. For correction of procedural losses [6, 7-3H2] 2-hydroxyestrone and [6, 7-3H2] 2-methoxyestrone are used as internal standards. The method is highly specific as checked by comparison to a double-isotope-derivative method and a newly developed gas chromatography-mass spectrometry procedure. Using this method the urinary excretion of 2-hydroxyestrone and 2-methoxyestrone was studied in children, men, cycling, pregnant and postmenopausal women. Special interest was focussed on the molar ratios of 2-hydroxyestrone to 2-methoxyestrone and the so called "total estrogens" which vary markedly within the different groups investigated. The excretion of 2-hydroxyestrone is especially favoured in women during the menstrual cycle and pregnancy.
Adult↗
Activity of cefuroxime, cefoxitin and amikacin against Serratia marcesens.
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Amikacin↗
Radioimmunoassay for 2-methoxyoestrone in human plasma.
A bovine serum albumin conjugate of 2-methoxyoestrone was used for the preparation of highly specific antibodies in rabbits. Cross-reactivity for catecholoestrogens and monophenolic steroids was below 0.3%. Only 2-methoxyoestradiol cross-reacted with 44%. An assay procedure for the determination of unconjugated and conjugated 2-methoxyoestrone in human plasma is described. The following mean plasma concentrations (pg/ml) were found (unconjugated/conjugated): children 61/1130, young men 74/1320, elderly men 109/1260, cycling women 131/1040, post-menopausal women 102/1420, and pregnant women 3980/5850.
Adolescent↗
Radioimmunoassay of 2-hydroxyestrone.
Under the protection of ascorbic acid a 2-hydroxyestrone bovine serum albumin conjugate was prepared containing intact 2-hydroxyestrone as determined by gas chromatographymass spectometry. Using this antigen highely specific antibodies were raised in rabbits. Cross-reactivity for 2-hydroxyestradiol and 2-hydroxyestriol was 26 and 4.5%, respectively. An assay procedure of 2-hydroxyestrone in human plasma is described. Using special precautions the assay allows the determination of 2-hydroxyestrone in plasma samples of women (50-95 pg/ml), pregnant women (105-220 pg/ml), men (45-65 pg/ml) and children(20-40 pg/ml).
Adult↗
Prolonged serum elimination half-life of amoxycillin in the elderly.
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Aged↗
Formation of 2- and 4-hydroxyestrogens by brain, pituitary, and liver of the human fetus.
When [6,7-3H]estradiol was incubated with tissue homogenates of the brain, the pituitary, and the liver of two human female fetuses, a number of radioactive metabolites more "polar" than the incubated substrate were detected. Among these, the identification of two types of catecholestrogens, i.e. the 2- and 4-hydroxyestrogens, was of major interest. Compared on the basis of wet weight of tissues (250 mg), the conversion of estradiol to 2-hydroxyestrogens (2-hydroxyestradiol and 2-hydroxyestrone) was 0.8% in the frontal cortex, 1.0% in the hypothalamus, 2.1% in the pituitary, and 7.8% in the liver. For the first time, the formation of 4-hydroxyestrogens was demonstrated. The percentages of incubated estradiol hydroxylated at C-atom 4 (4-hydroxyestradiol and 4-hydroxyestrone) were 0.5 in the cortex, 0.4% in the hypothalamus, .1% in the pituitary, and 0.5% in the liver. The results show that fetal brain and pituitary tissue can hydroxylate estradiol in positions 2 and 4 to a similar extent, whereas in the liver, about 15 times more 2-hydroxy than 4-hydroxy compounds are formed. Moreover, the 2-hydroxylating capacity of the liver is definitely greater than that of the brain, whereas the 4-hydroxylating capacity is about the same as that of the brain.
Brain↗
Comparative studies on the metabolism of oestradiol in the brain, the pituitary and the liver of the rat.
Radioactive oestradiol was incubated with homogenates of hypothalamus, pituitary and liver and slices of cortex, hippocampus, hypothalamus, pituitary and liver of ovariectomized rats. 2- and 4-substituted oestrogens were the main metabolites in the brain and were found in the same proportions. In the liver only the 2-substituted oestrogens were the main metabolites, while the 4-substituted ones were of minor quantitative importance. On the basis of wet weight the 2-hydroxylating capacity of the liver was approximately 50 fold greater than that of the brain and the 4-hydroxylating capacity about the same as that of the brain. Only slight differences in the 2- and 4-hydroxylating capacity of various brain areas were observed, although apparently the hypothalamus and the pituitary were more active in the formation of catecholestrogens than the cortex and the hippocampus.
Animals↗