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Background: Nesfatin-1 is a polypeptide encoded in the N-terminal region of Nucleobindin2 (NUCB2), expressed in the hypothalamus, pancreatic islets, gastric endocrine cells and adipocytes. Recent studies indicate its role in regulation of satiety and stimulation of insulin secretion. We assessed the relationship between serum nesfatin-1/NUCB2 and selected metabolic risk factors in normoglycemic individuals. Materials and Methods: Study included 80 normoglycemic, non-obese (BMI <30 kg/m2) subjects aged 25-40 years (32 women, 48 men). Basic anthropometric parameters (weight, BMI, WHR) and blood pressure measurements were performed. Laboratory tests: fasting plasma glucose, glycated hemoglobin (HbA1c), lipid profile, insulin, CRP, apolipoproteins AI and B were measured on automatic analyzers (Abbott Architect ci8200, Roche Cobas e411). Adiponectin and nesfatin-1/NUCB2 were assayed by commercially available ELISA kits (BioVendor R&D, Phoenix Pharmaceuticals Inc.). Results: Nesfatin-1/NUCB2 levels ranged 0.53- 14.38 ng/mL and were significantly higher in women compared to men (1.28 vs. 0.82 ng/mL; p=0.02). In men nesfatin-1/NUCB2 correlated negatively with glucose (R= -0.51; p=0.009), insulin (R= -0.33; p=0.038) and HOMA-IR (R= -0.42; p=0.027), while inverse relationship was observed in women. Multivariable regression analysis with glucose, insulin and HOMA-IR in females and with glucose, HOMAIR and adiponectin in males explained 87% and 32% of nesfatin-1/NUCB2 variability. Conclusions: Association of serum nesfatin-1/ NUCB2 with metabolic risk factors differs essentially by gender, however this issue requires further investigation in large, population-based study. [ABSTRACT FROM AUTHOR]

In this work, we describe the complex formation and radiochemistry of the cyclen-based chelator DOTI-Me bearing four methylimidazole arms. Radiolabeling properties were evaluated for 52g Mn, 64 Cu, 68 Ga, 111 In, 161 Tb, and 177 Lu, and DOTI-Me showed distinct differences to the structurally related H 4 DOTA. While radiochemical conversions (RCCs) for 52g Mn and 111 In were comparable to those of H 4 DOTA, DOTI-Me was not suited for 68 Ga. Conversely, quantitative RCCs were achieved for 64 Cu at ambient temperature, while elevated temperatures were required for complexation with H 4 DOTA. For 161 Tb and 177 Lu, good but not quantitative RCCs were obtained with DOTI-Me. With the exemption of 68 Ga 3+ , radiolabeled complexes showed high stability in ligand challenge experiments and in human serum. X-ray analysis of the nonradioactive complexes revealed the formation of 8-coordinate Mn 2+ and In 3+ DOTI-Me complexes. Cu 2+ adopted a unique distorted square-pyramidal 2 + 3 with the neutral DOTI-Me ligand and a Jahn-Teller distorted 4 + 2 coordination geometry for the diprotonated H 2 DOTI-Me 2+ cation, respectively. For Zn 2+ , the complex with HDOTI-Me + showed a distorted 4 + 3 pentagonal bipyramidal geometry. Summarizing, the ligand DOTI-Me may be an interesting alternative to H 4 DOTA for 52g Mn, 64 Cu, 111 In, 161 Tb, and 177 Lu, covering diagnostic as well as therapeutic radionuclides. Further studies of targeted radiopharmaceuticals based on the DOTI-Me scaffold in combination with the set of radiometals presented herein are thus warranted.

Background: Fructose acutely raises serum uric acid in normal subjects, but the effect in subjects with metabolic syndrome or subjects with chronic kidney disease is unknown. The aim of the study was to evaluate changes in serum uric acid during the fructose tolerance test in patients with chronic kidney disease, metabolic syndrome with comparison to healthy controls., Methods: Studies were performed in 36 subjects with obesity (body mass index >30) and metabolic syndrome, 14 patients with stage 3 chronic kidney disease, and 25 healthy volunteers. The fructose tolerance test was performed in each patient. The change in serum uric acid during the fructose challenge was correlated with baseline ambulatory blood pressure, serum uric acid, metabolic, and inflammatory markers, and target organ injury including carotid intima media thickness and renal resistive index (determined by Doppler)., Results: Absolute serum uric acid values were highest in the chronic kidney disease group, followed by the metabolic syndrome and then healthy controls. Similar increases in serum uric acid in response to the fructose tolerance test was observed in all three groups, but the greatest percent rise was observed in healthy controls compared to the other two groups. No significant association was shown between the relative rise in uric acid and clinical or inflammatory parameters associated with kidney disease (albuminuria, eGFR) or metabolic syndrome., Conclusions: Subjects with chronic kidney disease and metabolic syndrome have higher absolute uric acid values following a fructose tolerance test, but show a relatively smaller percent increase in serum uric acid. Changes in serum uric acid during the fructose tolerance test did not correlate with changes in metabolic parameters, inflammatory mediators or with target organ injury. These studies suggest that acute changes in serum uric acid in response to fructose do not predict the metabolic phenotype or presence of inflammatory mediators in subjects with obesity, metabolic syndrome or chronic kidney disease., Trial Registration: The study was registered in ClinicalTrials.gov. Identifier : NCT01332526. www.register.clinicaltrials.gov/01332526.

Background: The mechanism that underlies the association between low 25-hydroxyvitamin D [25(OH)D] and hypertension is not well understood; it seems to involve regulation of the renin-angiotensin-aldosterone system and the impact on endothelial function, cardiac remodeling, and subclinical organ damage. Vitamin D supplementation presents an ambiguous effect on endothelial function and arterial stiffness. We assess serum 25(OH)D3, biomarkers of endothelial dysfunction (soluble intercellular adhesion molecule [sICAM], C-reactive protein [CRP], homocysteine [Hcy]) and subclinical organ damage in adults with newly diagnosed untreated hypertension., Methods: Patients were classified based on ambulatory blood pressure monitoring: 98 had hypertension, whereas in 60 persons BP was normal. Laboratory assays including serum 25(OH)D3, hsCRP, Hcy, sICAM, glucose, insulin, lipids, echocardiography, pulse wave velocity (PWV), intima-media thickness (IMT), and left-ventricular mass (LVM) measurements were performed., Results: 25(OH)D3 was significantly lower in hypertensive patients. The logistic regression analysis indicated that 25(OH)D3 reduced the probability of hypertension occurrence after adjusting for body mass index (BMI). 25(OH)D3 in those with hypertension correlated significantly with systolic BP (SBP; r = -0.39), PWV, IMT (r = -0.33), and diastolic BP (r = -0.26). Multiple regression analysis in patients with hypertension revealed that 25(OH)D3 and sICAM accounted for up to 27% of SBP variation after adjusting for age, BMI, and smoking. 25(OH)D3 and either PWV or IMT accounted for 23% of SBP variation. The impact of 25(OH)D3 was 10%., Conclusion: The impact of 25(OH)D3 on SBP variation, mediated by its effect on endothelial dysfunction and subclinical organ damage, is modest but significant.

Fructose is a sugar present in sucrose, high-fructose corn syrup, honey, and fruits. Fructose intake has increased markedly in the last two centuries, primarily due to increased intake of added sugars. Increasing evidence suggests that the excessive intake of fructose may induce fatty liver, insulin resistance, dyslipidemia, hypertension, and kidney disease. These studies suggest that excessive intake of fructose might have an etiologic role in the epidemic of obesity, diabetes, and cardiorenal disease.

Glucose intolerance, insulin resistance and hyperinsulinemia are common findings in end-stage renal disease patients. Parathormone (PTH) and vitamin D3 are linked with disturbances of glucose metabolism. Glycated hemoglobin (HbA1c) reflects long-term glycemic control. HbA1c is a marker of increased risk of death in diabetic patients but also in general population. The aim of the study was to investigate the influence of 1,25(OH)2D3 therapy on long-term control of glycemia in hemodialyzed (HD) patients with severe secondary hyperparathyroidism (SHP). Eight HD patients with SHP (PTH=1088.6+/-472.2) were given intravenous 1,25(OH)2D3 1-2 microg thrice a week, for 12 weeks (mean dose 4.5 microg/week). At baseline and after 12 weeks fasting blood was sampled for: glucose, insulin, HbA1c, PTH. Insulin/glucose ratio (I/G) was calculated as marker of insulin resistance. Results were compared with 14 healthy volunteers (controls) matched for age, sex and BMI. At baseline I/G was higher in HD vs controls 0.110+/-0.045 vs 0.073+/-0.021 (p = 0.02), and of borderline significance at follow-up (0.106+/-0.053, p=0.05 vs controls). PTH decreased significantly to 506.1+/-646.3 (p<0.02) during therapy. Significant decrease of HbA1c in HD patients was observed (5.84+/-0.40 vs 5.13+/-0.51; p=0.01), while fasting glucose, insulin and I/G did not change significantly. Intravenous 1,25(OH)2D3 therapy is successful, even in patients with severe secondary hyperparathyroidism. Significant decrease in HbA1c with stable insulin concentration may indicate positive impact of intravenous 1,25(OH)2D3 therapy on long-term glucose metabolism.

Sunlight UV plays an important role in synthesis of active vitamin D3. Vitamin D3 concentration depends on seasonal sunlight exposure. It was not state, whether these changes may act on secondary hyperparathyroidism (SHP) in hemodialysis (HD) patients. The aim of our analysis was to assess the relationship between seasons and parameters of Ca-P metabolism in HD patients with SHP. We studied 30 pts (F = 17, M = 13), aged 20-72 years (mean 49 +/- 13), duration of HD therapy 3-132 months (mean 54.4 +/- 43.7), treated with alphacalcidol (1 alpha OHD3) due to SHP. Blood was collected for PTH, Ca, P concentrations in January (1), April (IV), July (VII) and October (X); also doses of CaCO3 and 1 alpha OHD3 were analyzed. The day duration was: 7 hours and 51 minutes (I), 12.53 (IV), 16.37 (VII) and 11.39 (X), respectively. PTH concentration was significantly higher in I vs IV (882 +/- 588 vs 691 +/- 511 pg/ml, p < 0.05) and higher in X vs VII (831 +/- 600 vs 701 +/- 525 pg/ml, p < 0.05), despite drug dosage did not differ. Calcium concentration was lower in I vs IV and X, and phosphate concentration was lower in I compared to IV, VII i X. These changes suggest presence of seasonal rhythm of PTH concentration in HD patients with SHP. When assessing the effectiveness of SHP therapy, the season of the year when PTH concentration was tested should be taken into account.

The essential arterial hypertension is the second (after diabetes mellitus) cause of chronic renal failure which means a great social and economic burden to the society. It is well known that hypertension is a metabolic syndrome resulting in tissue injury. We tried to investigate the possible influence of some metabolic disturbances on renal function in nontreated essential hypertension. We have compared 25 patients with nontreated essential hypertension (11 women, 14 men) with 14 healthy volunteers (7 women, 7 men) matched for age. The patients' group was characterized by significantly higher urine excretion of NAG (N-acetyl-beta-D-glucosaminidase) (2.75 +/- 1.69 vs 1.82 +/- 1.46 p < 0.05) and a tendency to significantly higher urine fractional sodium excretion without significant difference in albumin excretion. These findings suggest that the tubular damage is present. We noticed the negative linear correlation between mean arterial pressure and (MAP) and NAG urine excretion in the group of hypertensive patients which may reflect the renal ischemia in tubulo-interstitial pathology. Our data suggests that in nontreated arterial hypertension the renal blood flow disturbances are the important cause of the deterioration of tubular function (which are earlier to glomerular damage).