[Captopril-induced liver dysfunction].

Captopril is widely used for congestive heart failure and arterial hypertension. Its main side effects are cough, neutropenia, and renal injury. Liver dysfunction has rarely been described. We present a 71-year-old man with an acute myocardial infarction who developed high fever and progressive disturbance of liver function tests, hepatocellular and cholestatic, after beginning captopril. When other, more likely causes for his condition were ruled out, captopril was discontinued and the fever and liver dysfunction then quickly resolved. We recommend periodic laboratory follow-up in patients treated with angiotensin-converting enzyme inhibitors.

Fluoro-clomiphene and its synthetic precursors: synthesis and receptor binding.

In an attempt to synthesize compounds with selective estrogen-receptor binding, fluoro- and amino-clomiphene were totally synthesized from benzyl chloride, and their estrogenic/antiestrogenic activity as well as that of some of their chemical intermediates was evaluated. The triazene prepared from the amino-clomiphene was converted into fluoro-clomiphene with 39% yield. In the uterotropic test, both amino- and fluoro-clomiphene exerted mild equipotent estrogenic activity, with minimal saturation doses being 50 and 100 micrograms/rat/day for three days. In the receptor binding test both derivatives demonstrated similar displacement, with an A50% value in the 10(-5) M range, as compared to 10(-6) M for clomiphene and 10(-9) M for diethyl-stilbestrol. This synthesis may be useful for the preparation of 18F-labeled clomiphene for biodistribution studies.

Synthesis and receptor-binding affinity of fluorotamoxifen, a possible estrogen-receptor imaging agent.

Aminotamoxifen was totally synthesized from p-nitrobenzoyl chloride via a Friedel-Crafts acylation. Then, by means of a Balz-Schiemann reaction, aminotamoxifen was converted into fluorotamoxifen. The triazene variation of this conversion, with a 25% yield, enables a rapid, one-step diazotization, incorporating a fluorine atom into the phenyl ring of the tamoxifen. This reaction may be useful for the preparation of low specific activity 18F-labeled tamoxifen, for distribution, and for estrogen-receptor studies. For these in vivo and in vitro studies, fluorotamoxifen was also synthesized from p-fluorobenzoyl chloride, and its chemical intermediates were compared with estradiol and hexestrol, for their receptor binding and competition, as well as for their uterotropic activity. It is demonstrated that tamoxifen and fluorotamoxifen are strong estradiol agonists and partial hexestrol agonists, while aminotamoxifen is a weak estradiol and hexestrol agonist.

Increased erythrocyte glutathione peroxidase activity in psoriatics consuming high-selenium drinking water at the Dead-Sea Psoriasis Treatment Center.

Erythrocyte selenium-dependent glutathione peroxidase activity was measured in psoriatic Danes, before and after their four-week balneological therapy at the Ein-Bokek International Psoriasis Treatment Center, on the Dead-Sea shore in Israel. The drinking water in Ein-Bokek was found to be rich in selenium, a trace element with anticarcinogenic properties and of great importance in human nutrition and health. The most reliable biological parameter for increase in selenium bioavailability is the erythrocytes' glutathione-peroxidase activity. As psoriasis is a proliferative skin disease, the activity of this enzyme was assayed in 35 psoriatic Danes and in 25 long-term local hotel workers, as well as in 34 volunteers drinking low-selenium water. The glutathione peroxidase activity in the psoriatic patients increased significantly during their four-week stay in Ein-Bokek. Erythrocyte glutathione peroxidase activity in the hotel workers was 50% higher than that in the healthy volunteers consuming low-selenium water. A possible role of selenium in psoriasis is suggested.

Sex-dependent organ distribution of radiopharmaceuticals: effect of hormones on localization of acetyl-103Ru-ruthenocene.

This paper demonstrates modification of organ distribution of a radiopharmaceutical, acetyl-103Ru-ruthenocene, by competing drugs. This radiopharmaceutical concentrates in kidneys of male Wistar rats 15-fold higher than in females of the same strain and age. This concentration in the male is age-dependent. Moreover, the retention of that radiopharmaceutical in male rats' kidneys is markedly reduced by pre-treatment of the rats with estradiol, and this effect is dose-dependent. Estradiol is competetively inhibiting the retention of acetyl-ruthenocene by the kidneys, the same effect also being obtained by tamoxifen, an anti-estrogen used clinically for regression of mammary carcinoma. Blocking the retention of acetyl-ruthenocene was also obtained by testosterone and cyproterone-acetate, as well as by ovariectomy, but the block after castration was partially compensated with time. Blood clearance of acetyl-ruthenocene is biphasic, with a first t 1/2 of about 12 h, and a second t 1/2 of about 48 h. The retention of the label is sex-specific also in mice, but only the female mice show a high adrenal affinity and significant changes in its organ distribution. These effects may be due to competition of acetyl-ruthenocene for steroid receptors, or due to its activation of enzymes that are responsible for its transformation into a bindable moiety.