Anastrozole is a comparatively simple, achiral benzyltriazole derivative, 2,2'-[5-(1H-1,2,4-triazol-1-ylmethyl)-1,3-phenylene]bis(2-++ +methylpropiononitrile), that inhibits human placental aromatase with an IC50 of 15 nM and elicits maximal activity in vivo in rats (inhibition of ovulation and androstenedione-induced uterine hypertrophy) and monkeys (lowering of plasma oestradiol) at 0.1 mg/kg p.o. At 30 times this dose, anastrozole does not elevate plasma 11-deoxycorticosterone in monkeys, and at 100 times this dose, does not affect plasma aldosterone levels or Na+/K+ excretion in rats, plasma K+ concentrations in dogs, or cause adrenal hypertrophy in rats or dogs. It therefore has no discernible effect on adrenocorticoid hormone synthesis in vivo at very large multiples of its maximally effective aromatase-inhibiting dose. At similar large multiples in rats it displays no oestrogenic, anti-oestrogenic, androgenic, anti-androgenic, progestogenic, glucocorticoid, antiglucocorticoid or mineralocorticoid activity. Anastrozole is thus a potent and highly selective aromatase inhibitor, with no intrinsic hormonal activities--a pharmacological profile particularly suitable for the treatment of breast cancer.

Adrenal Glands↗

PubMed1993

The effects on rat thyroid function of an hepatic microsomal enzyme inducer.

1. Following daily administration to male albino rats for 2 weeks, beta-naphthoflavone (25 and 60 mg kg-1, i.p.) and phenobarbitone (100 mg kg-1, p.o.) produced their characteristic patterns of induction of P450-related enzyme activities. beta-naphthoflavone also induced p-nitrophenol glucuronidation by 160% over controls, while phenobarbitone produced only a 45% induction of this conjugation activity. 2. beta-Naphthoflavone produced significant reductions in plasma thyroxine (T4) concentrations on days 4 and 16 and also decreased tri-iodothyronine (T3) on day 4. Thyroid-stimulating hormone (TSH) was significantly increased on day 16 by the higher dose of beta-naphthoflavone. Thyroid weight was significantly increased at both dose levels on day 16 and liver weight was significantly increased on both days 4 and 16. No histopathological changes were seen in the liver or pituitary, but 30% of the animals showed minimal to mild follicular epithelial hypertrophy of the thyroid gland. 3. Phenobarbitone had no effect on T4 concentrations, but significantly decreased T3 on day 4. TSH increased by 60% on day 16, but was not statistically significantly compared with controls. Thyroid weight was significantly increased on day 16 and liver weight was significantly increased on days 4 and 16. Mild to moderate thyroid follicular epithelial hypertrophy and moderate hepatocyte hypertrophy occurred in all animals. No histopathological changes were seen in the pituitary. 4. The early changes in T4 and/or T3 were probably due to increased hepatic clearance by induction of thyroxine glucuronidation with both compounds. Thyroid hypertrophy would be expected to follow as a result of activation of the hypothalamic-pituitary-thyroid axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

1H-NMR spectroscopy as a means of monitoring nephrotoxicity as exemplified by studies with cephaloridine.

1. Male albino rats were dosed intravenously with either 0.9% saline or cephaloridine in saline at doses of 650, 750 or 950 mg kg-1 d-1 for 7 d. 2. Urine analysis on day 3, after two doses of cephaloridine showed dose-related increases in glucose, total protein, N-acetyl beta-D-glucosaminidase, gamma-glutamyltranspeptidase, alkaline phosphatase and lactate dehydrogenase. 1H-NMR spectroscopy showed corresponding disturbed profiles of products of intermediary metabolism indicative of a disruption of renal function. 3. By day 6, after five doses of cephaloridine, analysis by both 1H-NMR and conventional methods showed that all indices had returned to normal. 1H-NMR was demonstrated to provide useful complementary information to conventional techniques on the time course of the onset of the nephrotoxicity and the recovery phase, and was at least as sensitive as conventional urine analysis.

Animals↗

PubMed1990

The relationship between medical students' locus of control and promotion of breast self-examination.

There is general agreement that medical school curricula should involve the teaching of preventive health behaviours. Locus of control is a personality variable that has been associated with health practices and may be associated with tendencies to promote health practices. Few significant relationships have been found correlating health locus of control beliefs with preventive health behaviours. This study investigated the health locus of control of medical students and their tendencies to talk about and teach breast self-examination to women patients. Women students' health locus of control and breast self-examination practices were also investigated. The authors conclude that health locus of control has little influence on the tendency of medical students to promote breast self-examination. Other factors apparently have more effect on the student doctor's tendencies to promote health practices.

Attitude of Health Personnel↗

PubMed1990

Passive protection of piglets by monoclonal antibodies against experimental infection with Actinobacillus pleuropneumoniae.

Mouse monoclonal antibodies 11C11 (an IgG) and 4A9 (an IgM), which combine with a superficial component of cells belonging, respectively, to serovars 1 or 3 of Actinobacillus pleuropneumoniae, were given intraperitoneally 24 hours before and intranasally one hour before two-week-old, colostrum-deprived piglets were exposed by the intranasal route to 10(9) viable cells of either strain Shope 4074 (serovar 1) or 2/10 (serovar 3). Compared with control piglets given phosphate buffered saline or the heterologous monoclonal antibody, this procedure conferred substantial protection against the development of peracute or acute pleuropneumonia. Protection against the experimental disease was somewhat less in other piglets to which monoclonal antibody 4A9 was given only by the intranasal route one hour before the organism was administered than in those given the antibody intraperitoneally 24 hours beforehand, although its effect was still significantly greater than in piglets given phosphate buffered saline only. These two monoclonal antibodies consequently offer means of investigating at the molecular level the pathogenesis of the disease associated with A pleuropneumoniae and the potential value of anti-idiotypes as immunising agents.

Actinobacillus Infections↗

PubMed1988

Assay of glutathione reductase in crude tissue homogenates using 5,5'-dithiobis(2-nitrobenzoic acid).

A method for assaying glutathione reductase (GSH; EC 1.6.4.2) in crude plant extracts is described. The method is based on the increase in absorbance at 412 nm when 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) is reduced by GSH. The effects of the following parameters on the assay were tested: various buffers, pH, buffer concentration, compounds commonly present in enzyme preparations, thiols, and the presence of another NADPH-dependent enzyme. The assay is more sensitive and less subject to interference than the widely used assay where NADPH oxidation is monitored. In particular, the specificity of DTNB allows assay of glutathione reductase in the presence of other NADPH-dependent enzymes and common protein extract contaminants.

Dithionitrobenzoic Acid↗

PubMed1988

Survey of practices in evaluating teaching in U.S. medical schools, 1978 and 1986.

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Education, Medical, Undergraduate↗

PubMed1988

Translocation of Sulfate in Soybean (Glycine max L. Merr).

Sulfate translocation in soybean (Glycine max L. Merr) was investigated. More than 90% of the sulfate entering the shoot system was recoverable in one or two developing trifoliate leaves. In young plants, the first trifoliate leaf contained between 10 to 20 times as much sulfate as the primary leaves, even though both types of leaf had similar rates of transpiration and photosynthesis. We conclude that most of the sulfate entering mature leaves is rapidly loaded into the phloem and translocated to sinks elsewhere in the plant. This loading was inhibited by carbonylcyanide m-chlorophenylhydrazone and selenate. At sulfate concentrations below 0.1 millimolar, more than 95% of the sulfate entering primary leaves was exported. At higher concentrations the rate of export increased but so did the amount of sulfate remaining in the leaves. Removal of the first trifoliate leaf increased two-fold the transport of sulfate to the apex, indicating that these are competing sinks for sulfate translocated from the primary leaves. The small amount of sulfate transported into the mesophyll cells of primary leaves is a result of feedback regulation by the intracellular sulfate pool, not a consequence of their metabolic inactivity. For example, treatment of plants with 2 millimolar aminotriazole caused a 700 nanomoles per gram fresh weight increase in the glutathione content of primary leaves, but had no effect on sulfate aquisition.

Journal Article↗

PubMed1987

Decoloration and solubilization of plant tissue prior to determination of 3H, 14C, and 35S by liquid scintillation.

A method is described for the decoloration and partial solubilization of plant tissue with 2% sodium hypochlorite. Following treatment of the digest with ammonia, the samples are suitable for the determination of 3H, 14C, and 35S by liquid scintillation counting. The color quenching is negligible and counting efficiencies are high: 30-40% for 3H and 90-95% for 14C.

Carbon Radioisotopes↗

PubMed1987

Urinary enzymes and protein patterns as indicators of injury to different regions of the kidney.

Acute experimental models of renal damage to the proximal tubular, glomerular, and papillary regions of the rat were produced by administration of hexachloro-1:3-butadiene (HCBD), puromycin aminonucleoside (PAN), and 2-bromoethylamine (BEA), respectively. Several routine indicators of nephrotoxicity, the enzymes alkaline phosphatase and N-acetyl-beta-glucosaminidase, and the molecular weight of protein excretion were determined on urine samples. Tubular damage produced by HCBD or BEA was discriminated both quantitatively and qualitatively from glomerular damage produced by PAN. The latter was characterized by a pronounced increase in protein excretion, especially proteins with molecular weight greater than 40,000 Da. In contrast, protein excretion in tubular damage was raised only slightly and characterized by excretion of proteins of a wide range of molecular weights. Proximal tubular damage caused by HCBD and papillary damage caused by BEA were distinguished both by conventional urinalysis (volume and specific gravity) and by measurement of the two urinary enzymes. Alkaline phosphatase and glucose were markedly and transiently elevated in proximal tubular damage and N-acetyl-beta-glucosaminidase showed a sustained elevation in papillary damage. It is concluded that both selective urinary enzymes and the molecular weight pattern of urinary proteins can be used to provide diagnostic information about the possible site of renal damage.

Animals↗

PubMed1985

Effect of a breast examination teaching unit in physical diagnosis on medical students' practices.

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Breast↗

PubMed1985

Stimulation of glutathione synthesis in photorespiring plants by catalase inhibitors.

The effect of various herbicides on glutathione levels in barley (Hordeum vulgare L.), tobacco (Nicotiana tabacum L.), soybean (Glycine max [L.] Merr.), and corn (Zea mays L.) was examined. Illumination of excised barley, tobacco, and soybean plants for 8 hours in solution containing 2 millimolar aminotriazole (a catalase inhibitor) resulted in an increase in leaf glutathione from 250 to 400 nanomoles per gram fresh weight to 600 to 1800 nanomoles per gram fresh weight, depending on the species tested. All of this increase could be accounted for as oxidized glutathione. Between 25 and 50% of this oxidized glutathione was reduced when plants were darkened for 16 hours, but there was no significant decline in total glutathione. Another catalase inhibitor, thiosemicarbazide, was as effective as aminotriazole in elevating glutathione in soybean but was less effective in barley and tobacco. Glyphosate, an inhibitor of aromatic amino acid biosynthesis, had no significant effect on glutathione levels in any of the plants examined. Whereas methyl viologen (paraquat), which is a sink for photosystem I electrons, caused oxidation of leaf glutathione in all of the plants but did not increase the total amount of glutathione present.

Journal Article↗