Kornélia Štefíková

Effects of Long-Term Cholecalciferol Supplementation on Mineral Metabolism and Calciotropic Hormones in Chronic Kidney Disease

Background: Data on the efficacy and safety of long-term vitamin D supplementation in chronic kidney disease (CKD) are scarce. We assessed the effects of the 12-month vitamin D3 treatment on mineral metabolism and calciotropic hormones in patients with CKD stages 2–4. Methods: Eighty-seven patients (mean age 66 years, men/women 33/54) were randomized to cholecalciferol treatment with either 5,000 or 20,000 IU/week. Serum calcium, phosphate, 25(OH)D3, 1,25(OH)2D3, PTH and urinary mineral concentrations were obtained at baseline and after 4, 8 and 12 months. Results: The median serum mineral concentrations were normal and not changed throughout the study. The number of hypercalciuric patients slightly increased with higher dose, but no sustained rise in calciuria was present. Vitamin D insufficiency/deficiency was revealed in 72 (83%) patients at baseline and 37 (43%) at month 12. The 25(OH)D3 levels increased more with higher dose; a rise in 1,25(OH)2D3 was less impressive. The parathyroid hormone (PTH) concentrations were reduced, but the number of subjects with PTH below the lower limit for CKD stage 3 increased equally with both doses. Conclusions: Vitamin D insufficiency/deficiency in CKD significantly improved after the 12-month cholecalciferol treatment, with higher dose being more effective and equally safe. Further studies of vitamin D3 effects on bone metabolism are warranted.

Effects of Trigonelline, an Alkaloid Present in Coffee, on Diabetes-Induced Disorders in the Rat Skeletal System.

Diabetes increases bone fracture risk. Trigonelline, an alkaloid with potential antidiabetic activity, is present in considerable amounts in coffee. The aim of the study was to investigate the effects of trigonelline on experimental diabetes-induced disorders in the rat skeletal system. Effects of trigonelline (50 mg/kg p.o. daily for four weeks) were investigated in three-month-old female Wistar rats, which, two weeks before the start of trigonelline administration, received streptozotocin (60 mg/kg i.p.) or streptozotocin after nicotinamide (230 mg/kg i.p.). Serum bone turnover markers, bone mineralization, and mechanical properties were studied. Streptozotocin induced diabetes, with significant worsening of bone mineralization and bone mechanical properties. Streptozotocin after nicotinamide induced slight glycemia increases in first days of experiment only, however worsening of cancellous bone mechanical properties and decreased vertebral bone mineral density (BMD) were demonstrated. Trigonelline decreased bone mineralization and tended to worsen bone mechanical properties in streptozotocin-induced diabetic rats. In nicotinamide/streptozotocin-treated rats, trigonelline significantly increased BMD and tended to improve cancellous bone strength. Trigonelline differentially affected the skeletal system of rats with streptozotocin-induced metabolic disorders, intensifying the osteoporotic changes in streptozotocin-treated rats and favorably affecting bones in the non-hyperglycemic (nicotinamide/streptozotocin-treated) rats. The results indicate that, in certain conditions, trigonelline may damage bone.

The Cell Surface Markers Expression in Postmenopausal Women and Relation to Obesity and Bone Status

The age-related changes and hormonal deprivation in postmenopausal women are associated with the immune response alteration. The excessive fat accumulation, local and systemic inflammation may lead to dysregulation in immune function and relevant health problems, including obesity and osteoporosis. We analyzed the expression of cell surface markers in the venous blood specimens, stained with fluorophores-conjugated monoclonal antibodies and analysed by multicolour flow cytometry. The significant changes of cytotoxic, naive, and memory T-lymphocytes, plasmacytoid dendritic cells (DCs) were in postmenopausal women versus fertile women. Body mass index (BMI) affected markedly the cell surface expression of CD265/RANK. Osteoporosis is linked to reduced percentage of plasmacytoid DCs, and elevated natural Treg cells (p < 0.05). The confounding factors such as women age, BMI, bone mineral density (BMD), waist size and tissue fat affect the expression of RANK on myeloid DCs and CD40L on T-lymphocytes that might be the immunophenotypic modulators after menopause.

A different effect of obesity on ECG in premenopausal and postmenopausal women

Both obesity and menopause are significant cardiovascular risk factors. In postmenopausal women the protective effect of estrogens is reduced and menopause is frequently associated with occurrence of other significant cardiovascular factors including obesity. This study was focused on evaluating the effect of obesity on the QRS complex in pre- and postmenopausal women. We present results of analysis of 199 electrocardiograms of pre- and postmenopausal women analyzed in relation to the body mass index within normal limits (BMI 20 to 24.9 kg/m2) and obesity (BMI > 30 kg/m2), respectively. Obesity in premenopausal women and menopause significantly affected both the electrical axis (EA) and maximum QRS spatial vector magnitude (QRSmax). The highest QRSmax and electrical axis values were observed in premenopausal lean women, and they were significantly higher as than in the premenopausal obese women, postmenopausal lean and obese women (QRSmax: 1.66 ± 0.4 mV, 1.17 ± 0.35 mV, 1.4 ± 0.46 mV, and 1.35 ± 0.39 mV, resp.). (EA: 56.4 ± 18.0°, 38.22 ± 18.38°, 45.82 ± 18.63°, and 36.75 ± 17.51°). The differences between obese premenopausal women, lean and obese postmenopausal women were not statistically significant. These differences were reflected in 12-lead ECG amplitude. The presence of additional cardiovascular risk factors did not affect the ECG parameters. Obesity significantly affected QRS complex in premenopausal women. This effect was comparable with the effect of menopause. Because all QRS complex changes were within normal limits, these results suggest that ECG evaluation in women should go beyond traditional diagnostic categories and consider the relationship between ECG changes and two cardiovascular risk factors - obesity and menopause.

Caffeine at a Moderate Dose Did Not Affect the Skeletal System of Rats with Streptozotocin-Induced Diabetes

Diabetes may lead to the development of osteoporosis. Coffee drinking, apart from its health benefits, is taken into consideration as an osteoporosis risk factor. Data from human and animal studies on coffee and caffeine bone effects are inconsistent. The aim of the study was to investigate effects of caffeine at a moderate dose on the skeletal system of rats in two models of experimental diabetes induced by streptozotocin. Effects of caffeine administered orally (20 mg/kg aily for four weeks) were investigated in three-month-old female Wistar rats, which, two weeks before the start of caffeine administration, received streptozotocin (60 mg/kg, intraperitoneally) alone or streptozotocin after nicotinamide (230 mg/kg, intraperitoneally). Bone turnover markers, mass, mineral density, histomorphometric parameters, and mechanical properties were examined. Streptozotocin induced diabetes, with profound changes in the skeletal system due to increased bone resorption and decreased bone formation. Although streptozotocin administered after nicotinamide induced slight increases in glucose levels at the beginning of the experiment only, slight, but significant unfavorable changes in the skeletal system were demonstrated. Administration of caffeine did not affect the investigated skeletal parameters of rats with streptozotocin-induced disorders. In conclusion, caffeine at a moderate dose did not exert a damaging effect on the skeletal system of diabetic rats.