Testosterone increases serum 1,25–dihydroxyvitamin D and insulin-like growth factor-I in hypogonadal men

The short-term metabolic effects of testosterone treatment on circulating levels of 1,25-dihydroxyvitamin D and insulin-like growth factor-I (IGF-I) were studied in 13 hypogonadal men. The study group included 11 men with Klinefelter's syndrome, with varying degree of androgen deficiency, and two men with secondary hypogonadism. Pretreatment levels of 1,25-dihydroxyvitamin D, vitamin D-binding protein and IGF-binding protein-I were all within the normal range. The levels of IGF-I were lower than normal in 5/11 of the Klinefelter patients and in one patient with GH-deficiency. Testosterone treatment increased circulating total 1,25-dihydroxyvitamin D significantly from 75 +/- 4 pmol l-1 (mean +/- SEM) to 86 +/- 4 (P less than 0.01) and the free 1,25-dihydroxyvitamin D-index from 1.95 +/- 0.11 to 2.39 +/- 0.12 (P less than 0.01). Serum levels of IGF-I increased from 117 +/- 22 micrograms/l to 143 +/- 23 (P less than 0.01) during androgen treatment. No significant effects on levels of IGF-binding protein-I were seen. It is concluded that androgen therapy increases the availability of 1,25-dihydroxyvitamin D and the level of IGF-I, which may be important links in the action of testosterone.     

Deleterious effects of low-dose oestrogen theraphy on coronary status in patients with prostatic cancer

The effects of oestrogen therapy and of orchidectomy on coronarystauts, as reflected by exercise ECG-testing before and afteryear of tretment, were assessed in a randomized study of patients(N=100) prostatic cancer. Oestrogen was given as polyestradiolphosphate 80 mg i.m. per month in combination with 150 µgor in pre-traetment exercise test results Twelve months afterstart of therapy the oestrogen group showed a significantlygreater depression of the ST-segment during maximal exercisein leads CH₂ (P<0.0005) and CH⁵)P<0.01) compared withthe pre-treatment depression. Twenty-five per cent (N=13) ofthe patients in the oestrogen group suffered cardiovascularcomplications during the yera the of therapy, whereas no suchcomplications were observed in the orchidectomy group. However,even the patients in the oestrogen group who had not sufferedcardiovascular complications had significantly greater depressionsof the ST-segment during exercise both in lead CH₂ (P<0.0005)and in CH₅ (P<0.05). There was no significant change in theST-segment level in the orchidectomy group twelve months aftersurgery. In summary, we found of an induction of myocardialishaemia during treatment with exogenous oestrogens at low dosagein patients with prostatic. This deleterious effect of oestrogenon the coronary status argues against oestrogen therapy, sinceoedtrogen has not been shown to be more beneficial than orhidectomyagainst prostatic carcinoma.     

Controlled Clinical Trial of Treatment with Cimetidine for Non-ulcer Dyspepsia

ABSTRACT The effect of cimetidine (1 g daily) and placebo was studied in a controlled clinical trial comprising 50 patients with non-ulcer dyspepsia in whom an organic abnormality responsible for the dyspeptic symptoms was not disclosed by a standardized and extensive examination programme. Reduction of symptoms occurred in 13 (54%) out of 24 patients treated with cimetidine and in 16 (62%) out of 26 treated with placebo. The difference was insignificant, as were the alterations in the individual dyspeptic symptoms between the groups. Only 6 patients (25%) on cimetidine and 8 (31%) on placebo treatment had a total relief of symptoms. Of these, all cimetidine-treated patients remained free from symptoms during the successive 3-month observation period, while the dyspeptic symptoms relapsed in 3 (38%) placebo-treated patients. Subsequent resumption of placebo treatment reduced the symptoms in all 3 patients, but only one became free from symptoms. Cimetidine does not seem to be superior to placebo in the treatment of non-ulcer dyspepsia in patients without any previous history of ulcer or without any sign on endoscopy of an active or previous ulcer disease.     

Subchronic Inhalation Study with Vinyl Fluoride: Effects on Hepatic Cell Proliferation and Urinary Fluoride Excretion

Subchronic Inhalation Study with Vinyl Fluoride: Effects onHepatic Cell Proliferation and Urinary Fluoride Excretion. BOGDANFFY,M. S., KEE, C. R., KELLY, D. P., CARAKOSTAS, M. C, AND SYKES,G. P. (1990). Fundam Appl Toxicol. 15, 394/406. Vinyl fluorideis used widely in the manufacture of fluoropolymers. Based inpart on the structural similarity of vinyl fluoride to the hepatocarcinogensvinyl chloride and vinyl bromide, a TSCA Section 4 test rulemandated the testing of vinyl fluoride for oncogenicity. Thisreport presents the results of a 90-day inhalation study inrats and mice with vinyl fluoride designed to set test concentrationsfor a subsequent oncogenicity study. Groups of 15 male and femalerats and mice were exposed 6 hr per day, 5 days per week forapproximately 90 days to target concentrations of 0, 200, 2000,or 20,000 ppm vinyl fluoride. Clinical chemical, hematological,and urine analyses were performed on rats after 45 and 90 daysof exposure. A hematological evaluation was performed on micefollowing 45 and 90 days of exposure. A complete gross and microscopicevaluation was conducted at the end of the study. After 93 dayson test, groups of five rats and five mice per sex were implantedwith osmotic minipumps containing [3H]thymidine and were exposedfor an additional 5 days to measure cell proliferation in liver,kidney, lung, and nasal cavity tissues. Results of the histopathological,clinical chemical, and hematological evaluations showed no significanteffects of vinyl fluoride exposure at any concentration followingeither 45 or 90 days of exposure. A concentration-related increasein fluoride ion in urine was observed in rats at 45 and 90 daysof exposure. A plateau in urinary fluoride excretion was observedat approximately 2000 ppm, suggesting saturation of vinyl fluoridemetabolism. Vinyl fluoride-related cell proliferation effectswere largely restricted to liver. Hepatic cell proliferationin male and female rats and mice was elevated at all concentrations.The response was similar at concentrations of either 2000 or20,000 ppm and was consistent with concentration-response relationshipsfor other haloethylenes. Taken together, the urinary fluorideexcretion and hepatic cell proliferation data suggest a mechanisticlink between the two effects. On the basis of these findingsand experience with other haloethylenes, concentrations of vinylfluoride to be tested for oncogenicity should be chosen suchthat the full linear range of the concentration-response curveis evaluated. The present study demonstrates through examplethe value of incorporating cell proliferation studies in standardtesting protocols     

Effects of chronic oestrogen treatment are not selective for uterine noradrenaline-containing sympathetic nerves: a transplantation study

Previous studies have shown that chronic administration of oestrogen during postnatal rat development dramatically reduces the total content of noradrenaline in the uterine horn, abolishes myometrial noradrenergic innervation and reduces noradrenaline‐fluorescence intensity of intrauterine perivascular nerve fibres. In the present study we analysed if this response is due to a direct and selective effect of oestrogen on the uterine noradrenaline‐containing sympathetic nerves, using the in oculo transplantation method. Small pieces of myometrium from prepubertal rats were transplanted into the anterior eye chamber of adult ovariectomised host rats. The effect of systemic chronic oestrogen treatment on the reinnervation of the transplants by noradrenaline‐containing sympathetic fibres from the superior cervical ganglion was analysed on cryostat tissue sections processed by the glyoxylic acid technique. In addition, the innervation of the host iris was assessed histochemically and biochemically. The histology of the transplants and irises was examined in toluidine blue‐stained semithin sections. These studies showed that after 5 wk in oculo, the overall size of the oestrogen‐treated transplants was substantially larger than controls, and histology showed that this change was related to an increase in the size and number of smooth muscle cells within the transplant. Chronic oestrogen treatment did not provoke trophic changes in the irideal muscle. Histochemistry showed that control transplants had a rich noradrenergic innervation, associated with both myometrium and blood vessels. Conversely, in oestrogen‐treated transplants only occasional fibres were recognised, showing a reduced NA fluorescence intensity. No changes in the pattern and density of innervation or in the total content of noradrenaline of the host irises were detected after chronic exposure to oestrogen. We interpreted these results to indicate that the effects of oestrogen on uterine noradrenaline‐containing sympathetic nerves are neither selective or direct, but result from an interaction between sympathetic nerve fibres with the oestradiol‐primed uterine tissue. A potential effect of oestrogen on the neurotrophic capacity of the uterus is discussed.