Effect of magnesium on granulocyte function and on the exercise induced inflammatory response.

Magnesium status is a well-known modulator of the immune system. In the present study we investigated the effect of magnesium on granulocyte signalling and function. Furthermore, we performed a double-blinded randomised study investigating the effect of a two-month magnesium supplementation period on the exercise-associated alterations in immune function. In vitro incubation of granulocytes in media of different magnesium composition resulted in significant changes in chemotactic peptide-induced calcium transients while basal calcium levels were not affected. Likewise, the stimulus-induced formation of free radicals was affected by extracellular magnesium while phagocytosis of granulocytes was not affected. In the second part of the study we investigated whether a two-month period of magnesium supplementation was able to diminish alterations in immune cell counts and functions after an exercise test until exhaustion. The magnesium status was similar in both human and placebo groups and did not change significantly after the supplementation period. Exhaustive exercise induced an activation of the immune system as indicated by an increase in granulocyte count and a post-exercise lymphopenia. In addition, chemotactic peptide-induced cellular calcium transients were enhanced post-exercise while oxidative burst and phagocytosis were decreased. These results suggest that magnesium is an important modulator of immune cell function under in vitro conditions. However, a magnesium supplementation seems to be unable to prevent any exercise-associated alterations in immune cell function in athletes with balanced magnesium status.     

Hormone replacement therapy increases serum 1,25-dihydroxyvitamin D: A 2-year prospective study

Osteoporosis is a common disorder in postmenopausal women, which is probably due to decreased ovarian function. Currently, hormone replacement therapy (HRT), involving administration of estrogen and progestogen, is successfully applied to reduce bone resorption. We studied the effect of HRT on 23 postmenopausal women. This consisted of a combination of 17-estradiol and dydrogesterone, on the serum level of 1,25-dihydroxyvitamin D (1,25(OH)₂D) after 0, 6, 12, and 24 months. We found mean serum concentrations (±SD) of 1,25(OH)₂D of 130.5 pmol/liter (46.1), 152.7 pmol/liter (45.1), 170.8 pmol/liter (64.0), and 155.2 pmol/liter (59.7), respectively. The baseline values in these women were found to be significantly lower than those during therapy (P0.005). No statistically significant differences were observed when comparing the estrogen-only phase with the combined estrogen-progestogen phase. It is concluded that HRT results in an increase in the serum 1,25(OH)₂D concentration which lasts for at least 2 years. This increase may partly explain the preventive effect of HRT on osteoporosis. Purthermore, these results suggest that dydrogesterone does not influence the estrogen-induced changes in serum 1,25(OH)₂D concentration.     

Methods and biomarkers for the diagnosis and prognosis of cancer and other diseases: towards personalized medicine.

The rapid development of new diagnostic procedures, the mapping of the human genome, progress in mapping genetic polymorphisms, and recent advances in nucleic acid- and protein chip technologies are driving the development of personalized therapies. This breakthrough in medicine is expected to be achieved largely due to the implementation of "lab-on-the-chip" technology capable of performing hundreds, even thousands of biochemical, cellular and genetic tests on a single sample of blood or other body fluid. Focusing on a few disease-specific examples, this review discusses selected technologies and their combinations likely to be incorporated in the "lab-on-the-chip" and to provide rapid and versatile information about specific diseases entities. Focusing on breast cancer and after an overview of single-nucleotide polymorphism (SNP)-screening methodologies, we discuss the diagnostic and prognostic importance of SNPs. Next, using Duchenne muscular dystrophy (DMD) as an example, we provide a brief overview of powerful and innovative integration of traditional immuno-histochemistry techniques with advanced biophysical methods such as NMR-spectroscopy or Fourier-transformed infrared (FT-IR) spectroscopy. A brief overview of the challenges and opportunities provided by protein and aptamer microarrays follows. We conclude by highlighting novel and promising biochemical markers for the development of personalized treatment of cancer and other diseases: serum cytochrome c, cytokeratin-18 and -19 and their proteolytic fragments for the detection and quantitation of malignant tumor mass, tumor cell turn-over, inflammatory processes during hepatitis and Epstein-Barr virus (EBV)-induced hemophagocytic lymphohistiocytosis and apoptotic/necrotic cancer cell death.     

Effect of a combination of isoflavones and Actaea racemosa Linnaeus on climacteric symptoms in healthy symptomatic perimenopausal women: a 12-week randomized, placebo-controlled, double-blind study

OBJECTIVE: To investigate the effects of a novel dietary supplement containing soy isoflavones and Actaea racemosa Linnaeus (formerly called Cimicifuga racemosa L.) on climacteric symptoms in healthy perimenopausal women. DESIGN: In a multicenter, randomized, placebo-controlled, double-blind study, 124 women experiencing at least five vasomotor symptoms every 24 hours were randomized to receive daily either a phytoestrogen-containing supplement (n = 60) or placebo (n = 64) for 12 weeks. The modified Kupperman Index and Greene Climacteric Scale, a visual analogue scale designed to measure quality of life and the daily number and severity of hot flushes, was used in the screening period and in weeks 6 and 12. Changes in these scores from baseline were calculated. RESULTS: At weeks 6 and 12, all scores in both groups had improved compared with baseline, though the overall difference in scores between the groups was not statistically significant. CONCLUSION: The supplement containing soy isoflavones and A racemosa L. had no statistically significant effect on climacteric symptoms in perimenopausal women experiencing at least five vasomotor symptoms per day.     

Effects of transdermal and oral postmenopausal hormone therapy on vascular function: a randomized, placebo-controlled study in healthy postmenopausal women

OBJECTIVE: To compare the effect of transdermal and oral estrogen therapy, the latter with or without the addition of gestodene, on plasma concentrations of markers of endothelial function and on ultrasonographic parameters of vascular function in healthy postmenopausal women. DESIGN: In a 15-month, randomized, double-blind, placebo-controlled study, 152 healthy hysterectomized postmenopausal women received daily doses of placebo (n = 49), 50 microg of transdermal 17ss-estradiol (tE2, n = 33), 1 mg of oral E2 (oE2, n = 37), or 1 mg of oral estradiol combined with 25 microg of gestodene (oE2+ G, n = 33) for 13 cycles of 28 days, followed by four washout cycles with placebo in each group. At baseline and in cycles 4, 13, and 17, we measured plasma levels of endothelial markers and ultrasonographic markers of vascular function (pulsatility index [PI] and, at baseline and cycle 13, arterial stiffness). RESULTS: Compared with placebo, we found reductions in soluble vascular cell adhesion molecule (oE2, P < 0.01; oE2+ G, P < 0.001), sE-selectin (oE2 + G, P < 0.05), von Willebrand factor (tE2, P < 0.05), and divergent effects in PI and stiffness parameters in the carotid artery. We found no effect on PI in the retinal and femoral arteries, or on stiffness parameters in the femoral and brachial artery. CONCLUSIONS: Oral hormone therapy reduced plasma levels of adhesion molecules, whereas transdermal estrogen therapy reduced von Willebrand factor. Effects on ultrasonographic parameters of vascular function in the carotid artery were inconclusive.     

Endometrial safety and tolerability of AERODIOL(R) (intranasal estradiol) for 1 year

Objective: the purpose of this study was to assess the endometrial safety and patient acceptability of a pulsed estrogen therapy provided by S21400 (intranasal 17 β-estradiol) in the treatment of postmenopausal symptoms. Design: postmenopausal women (n=408) entered an open-label, community based, multicentre trial. Patients received S21400 plus sequential (>90% of patients) or continuous progestogen. Treatment was initiated with a standard daily dose of 300 μg but dose adaptation was possible every 3 months from 150 to 600 μg daily. Endometrial biopsies were performed at entry and at 12 months, and bleeding patterns were recorded at 3-monthly intervals throughout the trial. Results: 71% of patients received 300 μg per day S21400 throughout the study, 3% had their dose decreased, 19% had their dose increased and 7% had their dose both decreased and increased. Three hundred and eleven biopsies were obtained after 12 months of treatment, there were no cases of endometrial hyperplasia. The 95% confidence interval [CI] for the rate of incidence was 0–1.2%. Cyclical bleeding occurred in 82% of sequential treatment cycles. Unexpected bleeding occurred in 5% of the treatment cycles. Presence of unexpected bleeding varied according to the treatment regimen, 15 and 4% of the cycles with combined continuous and sequential regimen, respectively. Unexpected bleeding was mostly spotting. Nasal treatment was well accepted. Nasal symptoms (itching sensation, rhinorrhea and sneezing) were mostly mild in intensity and they led to treatment withdrawal in approximately 3% of patients. The rate of treatment continuation was 85% at 1 year. Conclusions: S21400, in combination with continuous or sequential progestogen, exhibits good endometrial safety and patient acceptability in postmenopausal women.