Association of Wnt Inhibitors, Bone Mineral Density and Lifestyle Parameters in Women with Breast Cancer Treated with Anastrozole Therapy.

AIM: To determine the levels of Wnt inhibitors in patients treated with aromatase inhibitors (AIs) prior to therapy and to investigate their association with bone mineral density (BMD) and lifestyle parameters. METHODS: 137 breast cancer patients were divided into a group treated with 1 mg of anastrozole and a group w/o anastrozole therapy. Serum concentrations of sclerostin and dickkopf1 (DKK1) were measured by ELISA. BMD was measured by dual-energy X-ray absorptiometry (DXA). Lifestyle factors were investigated by a self-reported questionnaire. RESULTS: Sclerostin was significantly higher in the AI-treated group (31.8 pmol/L vs. 24.1 pmol/L; p < 0.001), whereas DKK1 was significantly lower in the AI-treated group (24.3 pmol/L vs. 26.02 pmol/L; p < 0.001). Total hip and femoral neck BMD were significantly lower in the AI-treated group. CONCLUSION: AI treatment was associated with increased levels of sclerostin and decreased levels of DKK1.

Antioxidant Pre-Treatment Reduces the Toxic Effects of Oxalate on Renal Epithelial Cells in a Cell Culture Model of Urolithiasis.

Urolithiasis is characterized by the formation and retention of solid crystals within the urinary tract. Kidney stones are mostly composed of calcium oxalate, which predominantly generates free radicals that are toxic to renal tubular cells. The aim of the study is to explore possible effects of antioxidant pre-treatment on inhibition of oxidative stress. Three cell lines were used as in vitro model of urolithiasis: MDCK I, MDCK II and LLC-PK1. Oxidative stress was induced by exposure of cells to sodium oxalate in concentration of 8 mM. In order to prevent oxidative stress, cells were pre-treated with three different concentrations of l-arginine and vitamin E. Oxidative stress was evaluated by determining the expression of superoxide dismutase (SOD), osteopontin (OPN), and by the concentration of glutathione (GSH). In all three cell lines, pre-treatment of antioxidants increased cell survival. Positive correlation of SOD and OPN expression as well as GSH concentration was observed in all groups of cells. Our results indicate that an antioxidant pre-treatment with l-arginine and vitamin E is able to hamper oxalate-induced oxidative stress in kidney epithelial cells and as such could play a role in prevention of urolithiasis.

Association of nephrolithiasis and gene for glucose transporter type 9 (SLC2A9): study of 145 patients.

AIM: To investigate the association of nephrolithiasis and solute carrier family 2, facilitated glucose transporter, member 9 (SLC2A9), also known as glucose transporter type 9, Glut9. METHODS: A total of 145 participants were recruited in the period April-October 2008 from the Department of Mineral Research of the Medical School Osijek, Osijek, Croatia; 58 (40%) had confirmed nephrolithiasis and 87 (60%) were asymptomatic. Four single nucleotide polymorphisms (SNP) from the SLC2A9 gene were genotyped in both groups (rs733175, rs6449213, rs1014290, and rs737267). RESULTS: There was a weak but significant association of all 4 SNPs and nephrolithiasis (P=0.029 for rs733175; P=0.006 for rs6449213; P=0.020 for rs1014290, and P=0.011 for rs737267). Logistic regression in an age- and sex-adjusted model suggested that genotype C/T for rs6449213 had odds ratio for nephrolithiasis of 2.89 (95% confidence interval 1.13-7.40). This SNP explained a total of 4.4% of nephrolithiasis variance. CONCLUSION: Development of nephrolithiasis may be associated with SLC2A9 gene. Further studies are needed to clarify the role of SLC2A9 gene as a link between uric acid and nephrolithiasis.

Biochemical bone turnover markers: significance in patients with osteoporosis.

UNLABELLED: Osteoporosis is a systemic disease, which is characterized by reduced bone mass and microarchitectural deterioration of the bone tissue, resulting in an increased risk of fracture. Since osteoporosis is today a disease with high incidence rate, the aim of this study was to determine a correlation between bone mass density (BMD) and concentration of biochemical bone turnover markers--deoxypyridinoline (DPD) as a marker of bone resorption, and osteocalcin (OC) as a marker of bone formation. The study included 70 women between 33 and 76 years of age. In all women BMD was measured by Dual X-ray Absorptiometry (DXA) as a T-score. T-score was defined as the number of standard deviations of the bone mass density from the maximum bone mass density in young adults. According to T-score, patients were divided into three groups: patients with osteoporosis, patients with osteopenia and control group consisting of patients with normal T-score. DPD in urine and OC in serum were measured by a routine procedure. RESULTS: a negative correlation between BMD and concentration of bone turnover marker was discovered. One-way analysis of variance and Pearson correlation were used for statistical analysis, with a P value < 0.05 being considered significant. Although a negative correlation was discovered, we concluded that both procedures have a significant role in diagnosis and follow-up of patients with osteoporosis.

Metabolic and physico-chemical urolithiasis parameters in the first morning urine.

The 24-hour urine is golden standard for metabolic assessment of stone formers. However, due to the difficulties in collecting almost 1/3 of the samples can not be used for the analysis. Therefore, we analyzed first morning urine and calculated different risk indexes in order to asses possibility of using it in determining urolithiasis risk. Subjects were divided into 4 groups: male patients (n = 31, age 18-64), female patients (n = 31, age 25-63), male controls (n = 16, age 25-64) and female controls (n = 19, age 21-65). First morning urine pH, concentrations of calcium, magnesium, phosphate, sodium, potassium, chloride, citrate, urate, oxalate, creatinine and glycosaminoglycans were determined. Based on them, ionic concentrations and activity products of calcium oxalate and phosphate were calculated by EQUIL 2. In addition, different risk indices were calculated. The results showed that both patients and control groups had metabolic disorders, but the frequencies of occurrence were statistically independent. Significant difference in concentration of urinary constituents between corresponding patient and control groups was observed only for glycosaminoglycans in female subjects. Ca/Cit ratio and Baggio index could differentiate between both corresponding patients and control groups. The results indicate that interplay between stone formation inhibitors and promotors is responsible for urinary stone formation and that the first morning urine could be used in assessing urolithiasis risk and its prevention.

Urolithiasis and osteoporosis: clinical relevance and therapeutic implications.

Several clinical and epidemiological studies revealed increased bone turnover and lower bone mass in patients with urolithiasis. Bone mass loss is particularly evident in idiopathic calcium stone formers. However, pathogenetic mechanisms and factors implicated in bone loss in these patients are still unknown. Dietary calcium restriction, increased intake of salt and animal proteins, vitamin D receptor polymorphisms are likely risk factors, while role of inflammatory cytokines, osteopontin and prostaglandin mediated bone resorption is yet to be determined. Regarding treatment and prevention, it has been proven that calcium supplements and high calcium diet with the addition of potassium alkali have an important role in prevention and treatment of both, urolithiasis and osteoporosis. Thiazide diuretics reduce hypercalciuria in renal tubules, and in addition promote osteoblast differentiation. Finally, bisphosphonates, a commonly used drugs in treatment of osteoporosis, show the potential to inhibit calcium stone formation, whereas a possible protective effect of antioxidants in bone loss and renal injurie needs to be investigated further.

Prevalence of metabolic syndrome in the interior of Croatia: the Baranja region.

Metabolic syndrome (MS), a constellation of metabolic risk factors associated with development of cardiovascular diseases and Type 2 diabetes (T2D), has emerged as a public health problem of enormous proportions in developed and developing countries. We have reported previously its prevalence in several island populations of the Eastern Adriatic coast of Croatia. In spite of leading a relatively traditional life style pattern including adherence to a Mediterranean diet, the prevalence of MS in these populations is high and comparable to that in developed nations. However, data on prevalence of MS among the mainland Croatian populations is limited. Therefore, we conducted a study in an outbred population comprising of Croats, Hungarians and Serbs from the Baranja region of mainland Croatia. Although this is an ethnically heterogeneous population, the constituent groups exchange mates and therefore, are not reproductively isolated. The life style patterns are also similar. Overall prevalence of MS, assessed by the National Cholesterol Education Program (NCEP) criteria, is 40% (35% in males and 42% in females) with Body Mass Index (BMI) as the predictor of obesity and 42% (52% in males and 39% in females) with Waist Hip Ratio (WHR) as the predictor of obesity. It is likely that, in addition to genetic risk factors, a host of environmental factors that include dietary habits and relatively urban life style in a modernized society have influenced the levels of the constituent metabolic traits leading to an increased prevalence of MS.

Indications for synergetic and antagonistic effects between trace elements in the environment to human health.

The objective of this work was to investigate the interactions between the level of concentrations of Ca, V Cr, Mn, Fe, Ni, Cu, Zn, As and Pb in potable water, soil, vegetation and school children hair and disease incidences of neoplasms, diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism, endocrine, nutritional and metabolic diseases, mental and behavioral disorders and diseases of the circulatory system on the population groups which are homogeneously exposed to the environmental conditions. It was found that potable water among the other investigated aspects of the physical environment has the greatest impact on the public health. The environment-disease incidence interactions have been found for all investigated diseases groups. The results reported here emphasize the importance of the observation of the mutual effects of the environmental variables on the human health for the identification of their synergetic as well as antagonistic effects.