Zinc supplementation increases bone alkaline phosphatase in healthy men.

Zinc takes part in the metabolism of bone as a constituent of the matrix and as an activator of several metallo-enzymes. Animal in vitro and in vivo studies strongly suggest that zinc supplementation could stimulate bone formation and inhibit bone resorption but data in humans remain rare. The biological effects of 50 mg zinc given orally as gluconate in 20 healthy male volunteers were investigated in a 12 weeks double-blind placebo-controlled randomized trial. To investigate bone turnover, total alkaline phosphatases activity (ALP), bone specific alkaline phosphatase activity (BAPE) and BAP mass (BAP-M) concentration were measured as parameters of bone formation while urine calcium and C-terminal collagen peptide were determined as parameters of bone resorption. Samples were obtained in fasting subjects at baseline and after 6 and 12 weeks. In zinc treated subjects, a significant increase was observed at least after 12 weeks in total ALP (p < 0.01), BAP-M (p < 0.05) and BAP-E (p < 0.02). These parameters did not significantly change in the placebo group. Urine zinc/creatinine ratio significantly increased after 6 (p < 0.03) and 12 weeks (p < 0.04) in the zinc-treated group and was significantly different from the placebo group (p < 0.002). There was no significant effect of zinc supplementation on parameters of bone resorption. In conclusion, zinc supplementation at supraphysiological doses increased parameters of bone formation in healthy men while parameters of bone resorption remained unchanged.

Effect of estrogen replacement therapy with or without concomitant nonsteroidal anti-inflammatory drugs on pulsatility and resistance index of uterine arteries in healthy postmenopausal women.

OBJECTIVE: This study assesses the existence of a prostaglandin-mediated effect of estrogen on uterine arteries. METHODS: The pulsatility index (PI) and the resistance index (RI) of 10 postmenopausal women aged 50 to 65 who had not been on estrogen replacement therapy (ERT) for the 6 weeks preceding the study were measured at baseline level (T1), after randomization for either placebo or nonsteroidal anti-inflammatory drug (NSAID) (600 mg of Sulindac for one day) (T2), after 1 week of washout and cross-over (T3). They were then supplemented with ERT (transdermal system 50 micrograms/d, twice a week, Systen) for a period of 3 months. PI and RI of uterine arteries were assessed again while using ERT (T4), after either placebo or NSAID for one day (T5) and after 1 week of placebo-NSAID cross-over (T6). Assays of total cholesterol as well as the HDL, HDL2, LDL, triglycerides, endothelin-1, lipoprotein (a), estradiol and FSH were also obtained at baseline before receiving ERT and after 3 months of ERT. RESULTS: A small but significant increase of the PI was observed after NSAID intake as compared to the baseline measurement (P < .05), but no difference was observed for the RI. After estrogen treatment for 12 weeks, no difference was found between baseline measurements and the placebo intake or the NSAID intake. CONCLUSION: These results do not confirm a modulation by prostaglandin of the estrogen cardioprotective effect, although it is possible that the study lacks power.

Blood inflammatory response to inhaled endotoxin in normal subjects.

Previously we have reported that in asthmatics an inhalation of 20 micrograms lipopolysaccharide (LPS) produces a bronchial obstruction associated with an inflammatory blood response. The aim of the present study was to evaluate this response in normal subjects. Eight normal non-atopic subjects were challenged by inhalation of a solution containing 20 micrograms LPS (from Escherichia coli 026:B6) a week after bronchial challenge with control solution. The lung function response was evaluated by the changes in forced expiratory volume in one second (FEV1), in specific conductance and in airway resistance while the blood inflammatory response was evaluated by serial measures of total white blood cells (WBC) and polymorphonuclear neutrophils (PMN) count, luminol enhanced-chemiluminescence (luminol-CL, as a marker of the PMN degree of activation), C-reactive protein (CRP), haptoglobin, complement fraction C3, tumour necrosis factor-alpha (TNF-alpha) and adrenocorticotropic hormone (ACTH). No response in lung function was observed for 6 h after the LPS inhalation. The count in WBC and PMN increased 300 (P < 0.01) and 360 (P < 0.01) min after the LPS challenge associated with an increase in the level of luminol-CL (P < 0.001). This rise in luminol-CL level was significant at 120 min (P < 0.05) before any change in the PMN count. After 24 and 48 h the acute-phase protein CRP raised significantly (P < 0.01), the other proteins C3 and haptoglobin being unchanged. A slight increase in ACTH was observed 240 and 360 min (P < 0.05) after the LPS challenge while the TNF alpha detectable level was not modified.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular protection by estrogen: a hemodynamic mechanism?

Cardiovascular risk is higher in men than in women, and also more prevalent in postmenopausal than in premenopausal women, especially if not treated by estrogens. These differences may be due, in part, to a cardioprotective action of sex hormones, mainly estrogens. However, only a limited part of this protection may be attributed to metabolic modifications induced by replacement therapy with estrogen. Therefore, it remains to be determined which other cardioprotective mechanisms influenced by sex steroids might be involved. It has been demonstrated that the menopause is associated with an increase in uterine arterial pulsatility index, reflecting increased peripheral resistance, while the administration of estrogens has an opposite effect at this level. In Doppler studies, estrogen replacement therapy was also associated with an increase in stroke volume and flow acceleration in the aorta. This suggests a positive inotropic effect of estrogens. Using technetium scanning, it was found that women at an early phase of menopause have a stronger myocardial contractility than women of a similar age whose menopause is of longer duration. These effects of estrogens on hemodynamic characteristics might be controlled by vasoregulatory hormones such as endothelin(s) or endothelial-derived relaxing factor (EDRF), now identified as nitric oxide (NO). Indeed, sex-associated differences in endothelin have been observed. Such are some of the mechanisms by which estrogen administration might effect a cardiovascular protection. At the present time, however, conclusive data are not available.

Stimulation by thyrotropin, cholera toxin and dibutyryl cyclic AMP of the multiplication of differentiated thyroid cells in vitro.

Primary cultures of dog thyroid cells have been established. The cells originated from follicles and displayed differentiation characteristics of such cells: iodide trapping and organification, responsiveness of iodide organification and cyclic AMP accumulation to thyrotropin (TSH), induction of a two-dimensional follicular structure by TSH. TSH also stimulated the multiplication of these cells. The effect of TSH was detected with concentrations as low as 100 muU/ml and was reproduced with purified TSH. It was reproduced by cholera toxin (10 ng/ml) and dibutyryl cyclic AMP (10(-5) M). The data show that TSH, which stimulates the function of thyroid tissue, in vivo and in vitro, activates the multiplication of differentiated dog-thyroid follicular cells in primary culture, which suggests that this trophic effect is, partly at least, mediated by cyclic AMP.