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.     

Effect of 3-methylcholanthrene on the endocrine system and metabolism of the rat and its influence to retard growth of mammary tumors hitherto refractory

The repeated administration of 3-methylcholanthrene to adolescent rats resulted in (a) a profound, incomplete, and selective depression of certain hypophyseal functions; (b) decreased growth of transplanted mammary tumors; and (c) a retardation of body growth. Only the last mentioned effect was reversed by forced feeding. The retarded rate of body growth induced by 3-methylcholanthrene was prevented by the concurrent administration of dihydrotestosterone or progesterone, or by ovariectomy; rats so treated became overweight despite the injection of 3-methylcholanthrene. Phenolic estrogens intensified the retardation of body growth induced by 3-methylcholanthrene and emaciation resulted. The administration of 3-methylcholanthrene resulted in decreased gonadotrophin production by the pituitary and the ovaries were more drastically affected by the depression of pituitary activity than the adrenals were. The compound exerted differential effects on the pituitary glands of males and females respectively. Hormonal functions of both ovary and testis were decreased in rats treated with 3-methylcholanthrene but, whilst ovarian weight was much reduced, the size of the testis was not decreased and the germinal epithelium of the male was little affected by the treatment in most instances. There was a considerable reduction of the content of alkaline phosphatase in the breast of intact rats treated with 3-methylcholanthrene but atrophy of the mammary epithelium did not occur and hyperplasia of the mammary tree was often observed. The administration of 3-methylcholanthrene considerably slowed the growth of transplanted mammary tumors characterized by high dependence on hormones and the concurrent administration of gonadotrophin restored the growth rate of the tumors. The administration of 3-methylcholanthrene or androstan-17β-ol-3-one was only moderately effective in controlling the growth of transplanted mammary tumors characterized by low hormonal dependence; the combined administration of these compounds was highly efficacious in retarding the growth of these refractory tumors. 3-Methylcholanthrene partially retarded the growth of mammary fibroadenomas in hypophysectomized rats.     

Culprit-Only or Multivessel Percutaneous Coronary Stenting in Patients with Non-ST-Segment Elevation Acute Coronary Syndromes: One-Year Follow-Up

Objective: To investigate the major cardiac events at 1-year follow-up of multivessel versus culprit-vessel stenting in patients presenting with non-ST elevation acute coronary syndrome (NSTE-ACS) and multivessel disease (MVD).
Introduction: Percutaneous coronary intervention is a standard revascularization strategy for patients with NSTE-ACS. However, when these patients have MVD it is not clear whether multivessel (MVR) is superior to culprit-vessel revascularization (CVR).
Methods: We screened 1,100 consecutive patients with NSTE-ACS from an institutional database. Comparisons of 1-year outcomes between multivessel and culprit-vessel revascularized patients were made. The primary outcome was the composite (MACE) of death, myocardial infarction (MI), or any revascularization. Secondary end-points were the components of the composite end-point. Regression analysis was performed to detect predictors of MACE.
Results: A total of 609 patients were considered for this analysis: 204 (33.5%) and 405 (66.5%) had MVR and CVR treatment, respectively. The strategy adopted was based on a clinical decision. The incidence of MACE was lower in MVR (9.45% vs. 16.34%, P = 0.02) with lower revascularization rate (7.46% vs. 13.86%, P = 0.04) than in CVR. There was no difference in death (1.99% vs. 1.98%, P = 0.8) nor death/MI (2.49% vs. 3.22%, P = 0.8) between MVR and CVR, respectively. Multivariate analysis showed CVR as the only independent predictor of improved MACE (OR 0.66, CI95% 1.12–3.47, P = 0.01).
Conclusion: Multivessel stenting in patients with NSTE-ACS and multivessel disease using a clinical decision of treatment is associated with lower rate of MACE driven by lower repeat revascularization, compared with culprit-vessel stenting, without difference in rates of death or MI.