Clinical efficacy and safety of use of alfacalcidol and calcitriol in daily endocrinological practice.

This paper aims to discuss and compare 2 vitamin D derivatives available on the Polish market, alfacalcidol and calcitriol, in the context of their effectiveness and safety in endocrine patients. Both above-mentioned substances find a number of applications, including in hypoparathyroidism, which is one of the most common indications for their use. We would also like to draw the reader's attention to the fact that there are quite a lot of reports in the literature on the positive effect of alfacalcidol and calcitriol on maintaining bone mass and the risk of fractures, which may bring additional potential benefits to our patients.

Assessment of Wnt pathway selected gene expression levels in peripheral blood mononuclear cells (PBMCs) of postmenopausal patients with low bone mass.

The purpose of the study was to assess the expression of selected genes of the Wnt pathway: APC, AXIN1, CTNNB1, DKK1, GSK3ß, KREMEN1, SFRP1, and WNT1 in peripheral blood mononuclear cells (PBMC) of patients, selected in consideration of their bone mineral density (BMD), and the occurrence of low-energy fractures. The study involved 45 postmenopausal women, divided into four groups, according to BMD and fracture history. Measurements of laboratory parameters and RNA expression in PBMC cells were carried out in material, collected once at the inclusion visit. The densitometric examination was performed on all participants. In the analysis of the relative expression levels (RELs) of the studied genes in the entire population, we observed an overexpression for SFRP1 in 100% of samples and WNT1. In addition, the REL of DKK1, APC, and GSK3ß genes were slightly elevated versus the calibrator. In contrast, CTNNB1 and AXIN1 presented with a slightly decreased RELs. Analysis did not show any significant differences among the groups in the relative gene expression levels (p < 0.05) of particular genes. However, we have observed quite numerous interesting correlations between the expression of the studied genes and BMD, the presence of fractures, and laboratory parameters, both in the whole studied population as well as in selected groups. In conclusion, the high level of CTNNB1 expression maintains normal BMD and/or protects against fractures. It also appears that the changes in expression levels of the Wnt pathway genes in PBMCs reflect the expected changes in bone tissue.

Biomarkers, myocardial fibrosis and co-morbidities in heart failure with preserved ejection fraction: an overview.

The prevalence of heart failure with preserved ejection fraction (HFpEF) is steadily increasing. Its diagnosis remains difficult and controversial and relies mostly on non-invasive echocardiographic detection of left ventricular diastolic dysfunction and elevated filling pressures. The large phenotypic heterogeneity of HFpEF from pathophysiologic al underpinnings to clinical manifestations presents a major obstacle to the development of new therapies targeted towards specific HF phenotypes. Recent studies suggest that natriuretic peptides have the potential to improve the diagnosis of early HFpEF, but they still have significant limitations, and the cut-off points for diagnosis and prognosis in HFpEF remain open to debate. The purpose of this review is to present potential targets of intervention in patients with HFpEF, starting with myocardial fibrosis and methods of its detection. In addition, co-morbidities are discussed as a means to treat HFpEF according to cut-points of biomarkers that are different from usual. Biomarkers and approaches to co-morbidities may be able to tailor therapies according to patients' pathophysiological needs. Recently, soluble source of tumorigenicity 2 (sST2), growth differentiation factor 15 (GDF-15), galectin-3, and other cardiac markers have emerged, but evidence from large cohorts is still lacking. Furthermore, the field of miRNA is a very promising area of research, and further exploration of miRNA may offer diagnostic and prognostic applications and insight into the pathology, pointing to new phenotype-specific therapeutic targets.

Effects of physical activity on sclerostin concentrations.

Osteoporosis is a serious medical and socioeconomic problem of the 21st century. Mechanical load is a key regulator which controls bone formation and remodelling, with participation of osteocytes. Sclerostin is produced and released by mature osteocytes into bone surface, where it inhibits the conveyance of osteoblast proliferation and differentiation activating signals from mesenchymal cells, thus suppressing new bone formation. The goal of the study was an evaluation of the effects of a 12-week physical training programme on the levels of bone turnover markers [Sclerostin, Osteocalcin (OC), C-terminal telopeptide of type I collagen (ß-CTX)] in blood serum of women with osteopenia. MATERIALS & METHODS: The study included 50 women of the Regional Menopause and Osteoporosis Centre of the WAM Teaching Hospital, at the age of 50-75 years with the diagnosis of osteopenia, obtained on the basis of hip and/or lumbar spine densitometry (T-score from -1.0 to -2.5 SD). During the initial 12 weeks (between point 1 and 2), the patients maintained their previous, normal level of physical activity. During subsequent 12 weeks (between point 2 and 3), a programme of exercise was implemented. The programme included the interval training on a bicycle ergometer, three times a week for 36 minutes. During the entire study duration, all the patients received a supplementation of calcium (500 mg) and vit. D3 (1800 IU) once daily. Serum levels of OC, alkaline phosphatase (ALP), ß-CTX and sclerostin were assayed at 3 time points. RESULTS: After the course of the exercise cycle, the OC concentration was increased, sclerostin levels decreased, while no statistical differences were observed in ß-CTX levels vs. the period of physical inactivity. No correlations were found between sclerostin level changes and osteocalcin level changes during the training time, because of too small groups. Neither statistically significant were the differences in alkaline phosphatase, calcium and phosphorus levels. CONCLUSIONS: The obtained results emphasise the role of physical training as an effective stimulation method of bone formation processes in women with osteopenia. Sclerostin can be a marker of physical activity. < /p > < p >.

The role of selenium in thyroid gland pathophysiology.

It is now assumed that proper functioning of the thyroid gland (TG), beside iodine, requires also a number of elements, including selenium, iron, zinc, copper, and calcium. In many cases, only an adequate supply of one of these microelements (e.g. iodine) may reveal symptoms resulting from deficits of other microelements (e.g. iron or selenium). Selenium is accounted to the trace elements of key importance for homeostasis of the human system, in particular, for the proper functioning of the immune system and the TG. Results of epidemiological studies have demonstrated that selenium deficit may affect as many as one billion people in many countries all over the world. A proper sequence of particular supplementations is also worth emphasising for the significant correlations among the supplemented microelements. For example, it has been demonstrated that an excessive supplementation of selenium may enhance the effects of iodine deficit in endemic regions, while proper supplementation of selenium in studied animals may alleviate the consequences of iodine excess, preventing destructive-inflammatory lesions in the TG. This paper is a summary of the current knowledge on the role of selenium in the functionality of the TG.

Markers of increased atherosclerotic risk in patients with chronic kidney disease: a preliminary study.

BACKGROUND: The prevalence of chronic kidney disease is rising continuously. Cardiovascular disease is among leading causes of death and premature mortality of patients with chronic kidney disease. Even the earliest stages of chronic kidney disease are associated with higher risk of subsequent coronary heart disease. The aim of this study was to determine markers of increased risk of atherosclerosis in CKD. METHODS: The study group consisted of a total of 80 patients (20 patients with stage I/II CKD, 20 with stage III CKD, 20 stage IV CKD and 20 stage V/dialysis) and 24 healthy volunteers. Levels of proteins (osteoprotegerin, osteopontin, osteocalcin, matrix γ-carboxyglutamic acid protein, fetuin A, MMP-2, MMP-9, TIMP-1, TIMP-2) and biochemical parameters were measured to analyse their influence on atherosclerosis risk in CKD patients. Cardiac echocardiography was performed to assess structural integrity and function, presence of left ventricular hypertrophy and systolic and diastolic function dysfunction. RESULTS: This study shows that the prevalence of ventricular hypertrophy (95.3 %) and diastolic dysfunction (93.2 %) in CKD patients is high. Also E/E' ratio was significantly higher (13.6 ± 4.4, p = 0.001), tricuspid insufficiency (27.3 in CKD I/II vs. 71.4 in CKD V, p = 0.016), contractile dysfunction (33.3 in CKD I/II vs. 78.9 in CKD V, p = 0.040), mitral valve calcification (0 in CKD I/II vs. 28.6 in CKD V, p = 0.044) and aortic valve calcification (0 in CKD I/II vs. 61.9 in CKD V, p = 0.0008) were significantly more frequent in patients with CKD stage V/dialysis than in other groups. Only MMP-2, MMP-2/TIMP-2 ratio and TIMP-1 differed significantly between groups. CONCLUSIONS: This study shows high prevalence of ventricular hypertrophy and diastolic dysfunction in CKD patients. Contractile dysfunction, mitral and aortic valve calcification in HD patients were significantly more frequent than in patients with other CKD stages. Significantly increased levels of MMP-2, MMP-2/TIMP-2 ratio and lower TIMP-1 suggests that these factors may be involved in the pathogenesis of atherosclerosis in CKD patients.

The multi-biomarker approach for heart failure in patients with hypertension.

We assessed the predictive ability of selected biomarkers using N-terminal pro-brain natriuretic peptide (NT-proBNP) as the benchmark and tried to establish a multi-biomarker approach to heart failure (HF) in hypertensive patients. In 120 hypertensive patients with or without overt heart failure, the incremental predictive value of the following biomarkers was investigated: Collagen III N-terminal propeptide (PIIINP), cystatin C (CysC), lipocalin-2/NGAL, syndecan-4, tumor necrosis factor-α (TNF-α), interleukin 1 receptor type I (IL1R1), galectin-3, cardiotrophin-1 (CT-1), transforming growth factor ß (TGF-ß) and N-terminal pro-brain natriuretic peptide (NT-proBNP). The highest discriminative value for HF was observed for NT-proBNP (area under the receiver operating characteristic curve (AUC)=0.873) and TGF-ß (AUC=0.878). On the basis of ROC curve analysis we found that CT-1>152 pg/mL, TGF-ß<7.7 ng/mL, syndecan>2.3 ng/mL, NT-proBNP>332.5 pg/mL, CysC>1 mg/L and NGAL>39.9 ng/mL were significant predictors of overt HF. There was only a small improvement in predictive ability of the multi-biomarker panel including the four biomarkers with the best performance in the detection of HF-NT-proBNP, TGF-ß, CT-1, CysC-compared to the panel with NT-proBNP, TGF-ß and CT-1 only. Biomarkers with different pathophysiological backgrounds (NT-proBNP, TGF-ß, CT-1, CysC) give additive prognostic value for incident HF in hypertensive patients compared to NT-proBNP alone.

Biomarkers and echocardiographic predictors of myocardial dysfunction in patients with hypertension.

The study aimed to identify early echocardiographic and circulating biomarkers of heart failure (HF) in hypertensive patients with normal resting echocardiography. Echocardiography at rest and during exercise, and selected biomarkers were assessed in control group, dyspnea group, and HF group. On exercise dyspnea patients had lower early diastolic (E') and systolic (S') mitral annular velocity (12.8 ± 1.0 vs 14.9 ± 3.0 cm/sec and 9.3 ± 2.0 vs 10.9 ± 2.0 cm/sec, respectively), and higher E/E' ratio compared to control group (6.7 ± 1.0 vs 5.9 ± 1.0) (p < 0.05 for all comparisons). The level of N-terminal propeptide of procollagen type III (PIIINP) was significantly higher in dyspnea group than in controls (p = 0.01). Control and dyspnea patients had lower levels of cardiotrophin-1, cystatin C, syndecan-4, and N terminal-probrain natriuretic peptide than HF patients (all p ≤ 0.01). In multivariate analysis PIIINP (unadjusted odds ratio [OR] = 8.2, 95% confidence interval [Cl] 1.7-40.6; p = 0.001; adjusted OR = 8.7; 95%CI: 1.5-48.3; p = 0.001) and E/E' ratio on exercise (unadjusted OR = 1.8, 95%CI: 0.8-4.0; p = 0.033; adjusted OR = 2.0; 95%CI: 0.8-4.8; p = 0.012) were the only factors significantly associated with the presence of dyspnea. PIIINP is the first early biomarker for the HF development in patients with HA and normal resting echocardiography. Exertional echocardiography may indicate patients with incipient HF with preserved ejection fraction.

Analysis of vitamin D levels in patients with and without statin-associated myalgia - a systematic review and meta-analysis of 7 studies with 2420 patients.

INTRODUCTION: Vitamin D (vit D) deficiency may be associated with an increased risk of statin-related symptomatic myalgia in statin-treated patients. The aim of this meta-analysis was to substantiate the role of serum vitamin D levels in statin-associated myalgia. METHODS: The search included PUBMED, Cochrane Library, Scopus, and EMBASE from January 1, 1987 to April 1, 2014 to identify studies that investigated the impact of vit D levels in statin-treated subjects with and without myalgia. Two independent reviewers extracted data on study characteristics, methods and outcomes. Quantitative data synthesis was performed using a fixed-effect model. RESULTS: The electronic search yielded 437 articles; of those 20 were scrutinized as full texts and 13 studies were considered unsuitable. The final analysis included 7 studies with 2420 statin-treated patients divided into subgroups of patients with (n=666 [27.5%]) or without (n=1754) myalgia. Plasma vit D concentrations in the symptomatic and asymptomatic subgroups were 28.4±13.80ng/mL and 34.86±11.63ng/mL, respectively. The combination of data from individual observational studies showed that vit D plasma concentrations were significantly lower in patients with statin-associated myalgia compared with patients not manifesting this side effect (weighted mean difference -9.41ng/mL; 95% confidence interval: -10.17 to -8.64; p<0.00001). CONCLUSIONS: This meta-analysis provides evidence that low vit D levels are associated with myalgia in patients on statin therapy. Randomized controlled trials are necessary to establish whether vitamin D supplementation reduces the risk for statin-associated myalgia.

Markers of increased cardiovascular risk in patients with chronic kidney disease.

BACKGROUND: Epidemiological studies have shown that chronic kidney disease (CKD) is an important risk factor for atherosclerosis and cardiovascular disease (CAD). The aim of the study was to determine markers of increased risk of CAD and to achieve a better understanding of agents implicated in the process of atherosclerosis in CKD patients. METHODS: The study group consisted of a total of 139 patients with CKD while the control group comprised 45 healthy volunteers. Concentrations of osteoprotegerin, osteopontin, osteocalcin, matrix γ-carboxyglutamic acid (Gla) protein (MGP), fetuin A, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), ATP binding cassette transporter A1 (ABCA1), ATP binding cassette transporter G1 (ABCG1) and renalase were measured by the ELISA method. RESULTS: We observed decreased levels of fetuin A (control vs. CKD group: 37.5 vs. 33.2 ng/ml, p = 0.018), and increased concentrations of osteocalcin (control vs. CKD group: 9.1 ± 6.0 vs. 13.6 ± 10.3 ng/ml, p = 0.05), MMP-2 (113.1 ± 75.0 vs. 166.0 ± 129.9 ng/ml, p = 0.045), TIMP-2 (22.1 ± 5.1 vs. 25.4 ± 7,0 ng/ml, p = 0.005) and renalase (251.0 ± 157 vs. 316.1 ± 155.3 ng/ml, p = 0.026). In patients with CKD (in comparison to control group), left ventricle ejection fraction: 53.0 ± 3,5% vs. 48.5%, p = 0.012) and calcification of the aortic valve (9.5% vs. 39.8%, p = 0.008) were observed more frequently. CONCLUSIONS: Decreased levels of fetuin A and increased concentration of osteocalcin, renalase, MMP-2 and TIMP-2 suggest that these factors may be involved in the pathogenesis of CAD in patients with CKD. Significantly increased indices of cardiac hypertrophy and its dysfunction in patients with CKD are indicators of pathological mechanisms occurring in cardiovascular system in this group of patients.