Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study.

BACKGROUND: To measure bone mineral density (BMD) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid. PATIENTS AND METHODS: A phase 3 trial comparing tamoxifen, letrozole or letrozole+zoledronic acid in patients with hormone receptor-positive early breast cancer was conducted; triptorelin was given to premenopausal patients. Two comparisons were planned: letrozole versus tamoxifen and letrozole+zoledronic acid versus letrozole. Primary end point was the difference in 1-year change of T-score at lumbar spine (LTS) measured by dual energy X-ray absorptiometry scan. RESULTS: Out of 483 patients enrolled, 459 were available for primary analyses. Median age was 50 (range 28-80). The estimated mean difference (95% confidence interval [CI]) in 1-year change of LTS was equal to -0.30 (95% CI -0.44 to -0.17) in the letrozole versus tamoxifen comparison (P<0.0001) and to +0.60 (95% CI +0.46 to +0.77) in the letrozole+zoledronic acid versus letrozole comparison (P<0.0001). Bone damage by letrozole decreased with increasing baseline body mass index in premenopausal, but not postmenopausal, patients (interaction test P=0.004 and 0.47, respectively). CONCLUSIONS: In the HOBOE (HOrmonal BOne Effects) trial, the positive effect of zoledronic acid on BMD largely counteracts damage produced by letrozole as compared with tamoxifen. Letrozole effect is lower among overweight/obese premenopausal patients.

Effect of oral contraceptives on lacrimal fluid peroxidase activity in women.

Lacrimal fluid peroxidase has been supposed to be involved in the protection against oxidative damage to the ocular surface. Our recent findings showed the existence of significant cyclic variations in lacrimal fluid peroxidase activity that were positively correlated with those of 17beta-estradiol plasma levels throughout the menstrual cycle of fertile women. In the present study lacrimal fluid peroxidase activity of 8 healthy normocyclic women using low-dose oral contraceptives during the monthly cycle was determined. Data showed that low-dose oral contraceptives caused a decrease in lacrimal fluid peroxidase activity and a lack of its cyclic pattern with respect to the enzyme activity of 8 untreated age-matched women. Moreover, this result suggests that lacrimal fluid peroxidase activity could be regulated by estrogen.

Variations of lacrimal fluid peroxidase activity in female and male rats.

Previous research from this laboratory showed that human lacrimal fluid peroxidase has cyclic variations during the menstrual cycle, correlated with plasma levels of 17beta-oestradiol. In the present investigation, variations of enzyme activity and total protein content during the oestrous cycle of young adult female rats are analysed. Effects from circadian rhythm and a gender-related influence are also examined. In female rats, as in women, lacrimal fluid peroxidase activity shows cyclic variations; in fact, it significantly (p < 0.05) changes during the different phases of the oestrous cycle. In contrast, in males such variations do not occur. Thus, we suggest that gender seems to exert a significant influence on the secretion of this specific tear protein, probably by a direct effect of oestrogens.

Lacrimal fluid peroxidase activity during the menstrual cycle.

PURPOSE: The aim of this work was to investigate peroxidase activity in human tears during the various phases of the menstrual cycle. For comparative purposes saliva was also examined. METHODS: Tear fluids and saliva from 10 healthy volunteers 23-41 years of age (mean: 28.2 years), with regular menstrual cycles were sampled for the duration of at least two complete cycles. Menstrual cycles and ovulation periods were evaluated by measuring morning body temperature and hormone levels in plasma and urine. Unstimulated tears and unstimulated saliva were collected in the morning every two days. Peroxidase activity was monitored according to the 5,5'-dithiobis, 2-nitrobenzoic acid thiocyanate (Nbs-SCN) method and the protein content was determined by the Bradford method. RESULTS: Peroxidase activity in tears, expressed as U/mL, was significantly (p <.05) higher during the preovulatory and luteal phases with respect to the menses, whilst total protein content remained almost unchanged throughout all phases. A positive correlation was found between lacrimal fluid peroxidase activity and 17beta-estradiol plasma levels (p <.001). Salivary peroxidase activity did not show such estrogen-related changes. CONCLUSIONS: Our findings report cyclic variations in peroxidase activity in human tears during the menstrual cycle. Such cycling seems to reflect variations of 17 beta-estradiol plasma levels. These results suggest that a regulation of lacrimal fluid peroxidase by 17 beta-estradiol could be one possible cause for the female gender predilection in some ocular diseases, such as keratoconjunctivitis sicca.

A total body hyperthermia animal model for pharmacological studies.

Toxic side effects are the main drawback in localized and total body hyperthermia for the treatment of tumours. This paper reports a total body hyperthermia animal model which may be used as an experimental tool in the search for conditions or drugs capable of inhibiting the toxic effects of hyperthermia.