[111In]In-CP04 as a novel cholecystokinin-2 receptor ligand with theranostic potential in patients with progressive or metastatic medullary thyroid cancer: final results of a GRAN-T-MTC Phase I clinical trial.

INTRODUCTION: Medullary thyroid cancer (MTC) is a rare malignant tumour of the parafollicular C-cells with an unpredictable clinical course and currently suboptimal diagnostic and therapeutic options, in particular in advanced disease. Overexpression of cholecystokinin-2 receptors (CCK2R) represents a promising avenue to diagnostic imaging and targeted therapy, ideally through a theranostic approach. MATERIALS AND METHODS: A translational study (GRAN-T-MTC) conducted through a Phase I multicentre clinical trial of the indium-111 labelled CP04 ([111In]In-CP04), a CCK2R-seeking ligand was initiated with the goal of developing a theranostic compound. Patients with proven advanced/metastatic MTC or short calcitonin doubling time were enrolled. A two-step concept was developed through the use of low- and high-peptide mass (10 and 50 µg, respectively) for safety assessment, with the higher peptide mass considered appropriate for therapeutic application. Gelofusine was co-infused in a randomized fashion in the second step for the evaluation of potential reduction of the absorbed dose to the kidneys. Imaging for the purpose of biodistribution, dosimetry evaluation, and diagnostic assessment were performed as well as pre-, peri-, and postprocedural clinical and biochemical assessment. RESULTS: Sixteen patients were enrolled. No serious adverse events after application of the compound at both peptide amounts were witnessed; transient tachycardia and flushing were observed in two patients. No changes in biochemistry and clinical status were observed on follow-up. Preliminary dosimetry assessment revealed the highest dose to urinary bladder, followed by the kidneys and stomach wall. The effective dose for 200 MBq of [111In]In-CP04 was estimated at 7±3 mSv and 7±1 mSv for 10 µg and 50 µg CP04, respectively. Administration of Gelofusine reduced the dose to the kidneys by 53%, resulting in the organ absorbed dose of 0.044±0.019 mSv/MBq. Projected absorbed dose to the kidneys with the use of [177Lu]Lu-CP04 was estimated at 0.9±0.4 Gy/7.4 GBq. [111In]In-CP04 scintigraphy was positive in 13 patients (detection rate of 81%) with superior diagnostic performance over conventional imaging. CONCLUSION: In the present study, [111In]In-CP04 was shown to be a safe and effective radiopharmaceutical with promising theranostic characteristics for patients with advanced MTC.

Endothelial injury is closely related to osteopontin and TNF receptor-mediated inflammation in end-stage renal disease.

BACKGROUND: Endothelial dysfunction, inflammation and active mineralization are key processes involved in cardiovascular burden in end stage renal disease (ESRD). Serum (soluble) thrombomodulin (sTM) is an established marker of endothelial injury. PATIENTS: 80 patients in ESRD were recruited consecutively. Baseline distribution of sex, age, main comorbidities and Framingham score was similar. A biochemical panel including sTM, intact PTH (iPTH), interleukin-6 (IL-6), pentraxin 3 (PTX3), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), osteonectin (ON), soluble tumor necrosis factor receptor type 2 (TNFR2), transforming growth factor-ß (TGF-ß), hepatocyte growth factor (HGF), vascular endothelial growth factor receptor type 2 (sVEGFR2) and stromal cell-derived factor 1α (SDF1α) was investigated in each patient. Samples obtained while establishing haemodialysis (HD) access were stained for radial artery calcifications (RACs) with Alizarin red and examined histologically. RESULTS: After adjustment for HD status, sTM showed a significant positive correlation with serum creatinine, TNFR2, OPN, HGF, SDF1α, sVEGFR2, Pi, iPTH, FGF-23, OPG, OC and ON. In forward stepwise multiple regression, serum creatinine, TNFR2, and OPN were identified as significant, independent predictors of sTM. Grades 1-3 of RACs correlated with sTM (R = 0.50, p = 0.017), while grade 3 RACs were significantly associated with higher sTM (p = 0.02) than less advanced lesions. CONCLUSION: Among novel renal and cardiovascular biomarkers, OPN and TNFR2 are closely related to sTM. This may link endothelial damage, vascular remodeling and inflammation. Progression of RAC parallels a presumed compensatory rise in sTM, reflecting endothelial injury. sTM has an intricate role in endothelial function and potential clinical and prognostic applications.

Carboxylated and undercarboxylated osteocalcin in metabolic complications of human obesity and prediabetes.

BACKGROUND: Carboxylated osteocalcin (Gla-OC) participates in bone remodeling, whereas the undercarboxylated form (Glu-OC) takes part in energy metabolism. This study was undertaken to compare the blood levels of Glu-OC and Gla-OC in nonobese, healthy obese, and prediabetic volunteers and correlate it with the metabolic markers of insulin resistance and early markers of inflammation. METHODS: Nonobese (body mass index [BMI] <30 kg/m2 ; n = 34) and obese subjects (30

The use of selected neutrophil protein plasma concentrations in the diagnosis of Crohn's disease and ulcerative colitis - a preliminary report.

BACKGROUND: Difficulties in diagnosis of inflammatory bowel disease (IBD) motivate the search for new diagnostic tools, including laboratory tests. The aim of this study was to evaluate concentrations of the neutrophil (NEU) proteins leukocyte elastase (HLE-α1AT), lactoferrin and calprotectin as potential biomarkers used in the diagnosis and assessment of clinical activity of Crohn's disease (CD) and ulcerative colitis (UC). MATERIAL/METHODS: The study included 27 patients with CD, 33 patients with UC and 20 healthy controls. Plasma concentrations of calprotectin, lactoferrin and HLE-α1AT were measured using ELISA. RESULTS: In patients with CD higher concentrations of HLE-α1AT (64.3±43.1 vs. 30.1±7.7 ng/l, P<0.001), calprotectin (151.6±97.8 vs. 69.9±22.1 ng/l, P<0.001) and lactoferrin (243.2±102.0 vs. 129.7±32.7 ng/l, P<0.001) than in the control group were found. In patients with UC higher plasma concentrations of HLE-α1AT (62.0±30.9 vs. 30.1±7.7 ng/l, P<0.001), calprotectin (149.6±72.3 vs. 69.9±22.1 ng/l, P<0.001) and lactoferrin (242.6±107.5 vs 129.7±32.7 ng/l, P<0.001) than in the control group were found. HLE-α1AT/NEU and lactoferrin/NEU ratios in patients with UC were significantly higher compared with patients with CD. Calprotectin (P=0.010) and lactoferrin (P=0.023) levels were higher in patients with the active compared with inactive phase of CD. CONCLUSIONS: The diagnostic characteristics of plasma granulocyte protein concentrations indicate the usefulness of these tests in the diagnosis of IBD. Higher HLE-α1AT and lactoferrin/NEU ratios in patients with UC than with CD may suggest the usefulness of these ratios in differential diagnostics. Plasma calprotectin and lactoferrin levels may be useful in CD activity assessment.

Carboxylated and intact osteocalcin predict adiponectin concentration in hemodialyzed patients.

Purpose Disrupted bone metabolism in patients with chronic kidney disease (CKD) is associated with elevated concentrations of biochemical bone markers. Recently, animal studies show the role of osteocalcin in energy metabolism, which is partially confirmed in humans. The aim of our study was to evaluate the relationships between serum concentrations of bone markers and indices of energy metabolism in CKD patients on maintenance hemodialysis; in particular, the relationship between various forms of osteocalcin and adiponectin. Patients and methods The cross-sectional study included 155 hemodialyzed stage 5 CKD patients. Serum concentrations of glucose, insulin, adiponectin, bone alkaline phosphatase (bALP), tartrate resistant acid phosphatase (TRAP), carboxylated (cOC), undercarboxylated (ucOC), and intact osteocalcin (OC) were determined. Results In total cohort, bALP, TRAP, cOC, and ucOC negatively correlated with BMI. All analyzed bone markers positively correlated with adiponectin in total cohort and in men. In multiple linear regression analysis including all patients, log(cOC) and log(intact OC) were the only bone markers that predicted log(adiponectin) (beta = 0.22; p = 0.016 and beta = 0.26; p = 0.010) independently of sex, dialysis vintage, CRP, insulin, iPTH concentrations, BMI, and age. Conclusions Our data confirm the positive association between cOC, intact OC, and adiponectin concentrations in CKD patients on maintenance hemodialysis.

[Could the cytokines concentration be a marker of IBD activity and be useful in evaluation of IBD differentiation?]

Background: In inflammatory bowel disease (IBD) the imbalance between cytokines pro- and antinflammatory is observed. The aim of this study was the assessment of interleukin-10 (IL-10), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentration usefulness in the evaluation of the activity of ulcerative colitis (UC) and Cohn's disease (CD). Methods: 35 patients diagnosed with UC and 39 with CD were examined. The control group (CG) consisted of 35 healthy volunteers. Diagnosis of the disease was confirmed by videocolonoscopy and histopathological evaluation of intestinal biopsies. Disease activity of UC was assessed according to the Mayo Scoring System and by the Crohn Disease Activiti Index (CDAI) in CD patients. Among patients with UC 18 (51%) had severe, 14 (40%) moderate and 3 (9%) mild disease. Among patients with CD 7 (18%) was diagnosed with high, 27 (69%) moderate, and 5 (13%) with low activity of the disease. WBC, PLT, serum concentration of TNF-α, IL-6 i IL-10 were determined. Results: The average concentration of TNF-α in UC patients was: 14.3 (IQR=12.6), in CD: 12.6 (IQR=11.9), in the CG: 3.1 (IQR=1.7). The average concentration of IL-6 in UC was: 19.6 (IQR=21), in CD: 10.8 (IQR=7.6), in CG : 3.2 (IQR=1.6). The average concentration of IL-10 in UC was: 14.4 (IQR=5.9), in CD: 10.4 (IQR=9.3), in the CG: 3.3 (IQR=2.5). In the IBD TNF-α, IL-6 and IL-10 concentration was significantly higher than in CG. However, IL-10 was significantly higher in UC than CD. In patients with UC statistically significant positive correlation between the concentration of TNF-α, IL-6 and IL-10 and disease activity was noticed. There were no correlation between TNF-α, IL-6 and IL-10 concentration and CD activity. Conclusion: Determination of TNF-α, IL-6 and IL-10 serum concentration can be used for noninvasive evaluation of inflammation activity in patients with IBD. IL-10 concentration may be helpful in differentiation of UC and CD.

Plasma sICAM levels during standard exercise test are higher in postmenopausal women with mixed hyperlipemia. sICAM level in postmenopausal women.

Aim: Plasma sICAM, sVCAM, endothelin- 1 (ET-1), TNF-a, its soluble receptor levels and nitric oxide production evaluation during standard exercise test in postmenopausal women with mixed hyperlipidemia. Material and methods: 35 white, normotensive, non-smoking, postmenopusal women. Group A consisted of 24 women normal plasma cholesterol and triglicerides. Group B- 11 women hypercholesterolemic and hypertrigliceridemic. Basic fasting plasma FSH, 17b- -estradiol, total cholesterol, LDL-cholesterol, triglicerides, HDL-cholesterol were measured. Standard exercise test was carried out according to Bruce protocol. During the test blood samples were taken trice (prior to, at peak exercise, at15th minute of recovery). The sICAM, sVCAM, ET-1, TNF-a, its soluble receptor and secretion of nitric oxide were measured. Statistical analysis: Fisher test and t-Welch test were used. Results: There were no differences between groups A and B in mean plasma concentrations of FSH, estradiol and HDL-cholesterol. Mean plasma total cholesterol, triglicerides and LDL-cholesterol levels were higher in group B compared to group A. Plasma levels of sICAM prior to standard exercise test, at peak exercise and at the 15th minute of recovery were significantly lower in group A compared to group B. Mean plasma sVCAM levels did no differ between groups. NO3 plasma levels was significantly higher at peak exercise in group B compared to group A. There were no significant differences between groups in regard to mean plasma NO2, endothelin-1, TNF-a, and TNF-a receptor levels. Conclusion: Plasma soluble intracellular adhesion molecules levels are higher at rest and during exercise in postmenopausal women with atherosclerosis risk factors.

Relationship between fetuin-A, bone turnover and inflammatory markers concentrations in serum of maintenance hemodialyzed patients.

Introduction: Fetuin-A plays an important role in bone turnover and vascular calcification. Aim: The aim of the study was to assess the relationship between serum fetuin-A concentrations, inflammatory and bone turnover markers of patients on maintenance hemodialysis. Materials and Methods: The study was performed in 71 patients (21 women, 40 men) aged 60 ± 12 years on chronic dialysis because of end-stage renal failure for a period of 75 ± 57.2 months. The routine laboratory tests were performed with Modular P analyzer (Roche Diagnostics), serum concentrations of iPTH were measured using Nichols method, hsCRP and IL-6 using nephelometric techniques while fetuin-A, bone-specific alkaline phosphatase (bALP), fully carboxylated osteocalcin (cOC), undercarboxylated osteocalcin (ucOC), and fibroblast growth factor-23 (FGF-23) were measured using commercially available ELISA kits. Results: Concentrations of fetuin-A were significantly positively correlated with albumin (r=0.37, p=0.003) and negatively associated with patients age (r=26, p=0.04), log (iPTH) (r=0.31, p=0.02), log (CRP) (r=0.31, p=0.02), log (IL-6) (r=0.41, p=0.001), log (ucOC) (r=-0.29, p=0.02), and log (FGF-23) (r=0.27, p=0.04). Conclusions: 1. Patients on maintenance hemodialysis suffer from severe disturbances of bone turnover. 2. Low serum fetuin-A levels are associated with increase markers of bone turnover and inflammation.

Cardiovascular risk in chronic kidney disease patients: intima-media thickness predicts the incidence and severity of histologically assessed medial calcification in radial arteries.

BACKGROUND: The objective of the study was to determine the relationship between common carotid artery intima-media thickness (CCA-IMT) and histologically assessed calcification of radial artery in relation to clinical features and laboratory markers of bone and mineral metabolism, inflammation, and oxidative stress in patients with stage 5 chronic kidney disease (CKD). METHODS: The study comprised 59 patients (36 hemodialyzed, 23 predialysis). CCA-IMT was measured by ultrasonography; the biochemical parameters examined were assessed using routine laboratory methods, ELISA micro-plate immunoassays and spectrophotometry. Fragments of radial artery obtained during creation of hemodialysis access were cryosectioned and stained for calcifications using von Kossa method and alizarin red. RESULTS: Glucose, osteoprotegerin, pentraxin 3 and Framingham risk score significantly correlated with CCA-IMT. In multiple regression analysis, OPG positively predicted CCA-IMT. Radial artery calcifications were found in 34 patients who showed higher CCA-IMT (0.98 ± 0.13 vs 0.86 ± 0.14 mm; P = 0.006). Higher CCA-IMT values were also associated with more advanced calcifications. CCA-IMT and the presence of plaques in common carotid artery were positive predictors of radial artery calcifications, independent of dialysis status, Framingham risk score, CRP and Ca x Pi [OR for calcifications 2.19 (1.08-4.45) per 0.1 mm increase in CCA-IMT]. The presence of radial artery calcifications was a significant predictor of mortality, independent of dialysis status and Framingham risk score [HR 3.16 (1.03-9.64)]. CONCLUSIONS: In CKD patients, CCA-IMT examination can be used as a surrogate measure to assess the incidence and severity of arterial medial calcification which is associated with poor clinical outcome in these patients.

Differential associations of inflammatory and endothelial biomarkers with disease activity in rheumatoid arthritis of short duration.

OBJECTIVES: To estimate endothelial dysfunction in patients with rheumatoid arthritis (RA) of short duration in relation to disease activity based on the assessment of 28 joints (DAS28). METHODS: We studied 29 patients (22 women, mean age 41 (SD, 9) years) with RA of short duration and 29 healthy controls. The RA subjects were divided into those with low (DAS28: 2.6-5.1, n = 18) or high (DAS28 > 5.1, n = 11) disease activity. Exclusion criteria included clinically overt atherosclerosis and other coexistent diseases. Biochemical markers of inflammatory activation and endothelial dysfunction were measured. RESULTS: There were no significant intergroup differences in the majority of classical cardiovascular risk factors. High-sensitivity C-reactive protein, tumor necrosis factor- α , and interleukin-6 were increased in RA subjects. Compared to the controls, levels of soluble vascular cell adhesion molecule-1, von Willebrand factor, and pentraxin-3 were significantly elevated in RA subjects with low disease activity, exhibiting no further significant rises in those with high disease activity. Asymmetric dimethyl-L-arginine, soluble E-selectin, monocyte chemotactic protein-1, and osteoprotegerin were increased only in RA patients with high disease activity. CONCLUSIONS: Our findings might suggest a dissociation of pathways governing generalized and joint-specific inflammatory reactions from those involved in endothelial activation and inflammation within the vascular wall.

TGF-ß1 and granulocyte elastase in the evaluation of activity of inflammatory bowel disease. A pilot study.

INTRODUCTION: The aim was to assess the usefulness of TGF-ß1 and elastase in the evaluation of activity of ulcerative colitis (UC) and Crohn's disease (CD). MATERIAL AND METHODS: 32 patients diagnosed with UC, 31 with CD and 30 healthy volunteers were enrolled in this study. Diagnosis of the disease was confirmed by videocolonoscopy and histopathological evaluation of intestinal biopsies. Disease activity was assessed by use of the Mayo Scoring System for Assessment of Ulcerative Colitis Activity in UC patients and by CDAI in CD patients. hsCRP was determined by the immunonephelometric method, TGF-ß1 and elastase plasma concentration by ELISA. The results of the study were analyzed using Statistica and R statistical language. RESULTS: In UC a positive correlation between disease activity and platelet level, hsCRP and TGF-ß1 concentration was noted. Elastase concentration in UC patients was significantly higher than in CD, but there was no correlation with the activity of the disease. In CD patients we observed a positive correlation between disease activity and leukocytes, platelet levels and elastase concentration, and a very low correlation with hsCRP and TGF-ß1. DISCUSSION: Determination of TGF-ß1 can be used for evaluation of inflammatory activity in UC and it is connected with elevated concentrations of CRP and platelets. To a lower extent TGF-ß1 can also be used for evaluation of inflammatory activity in CD. Examination of elastase concentration may be useful in the assessment of CD activity. Plasma elastase concentration may be helpful in UC and CD differentiation. The preliminary results of this investigation seem promising; nevertheless, more studies are necessary.

[Uromodulin - can it be a new marker of kidney damage?]. / Uromodulina - czy moze byc nowym wskaznikiem uszkodzenia nerek?

Uromodulin (Tamm-Horsfall protein) is the most abundant protein excreted in the urine under physiological conditions. It is exclusively produced in the kidney and secreted into the urine via proteolytic cleavage. Its biological function is stillnot fully understood. Uromodulin has been linked to waterl electrolyte balance and to kidney innate immunity. Also, studies in knockout mice demonstrated that it has a protective role against urinary tract infections and renal stone formation. Mutations in the gene encoding uromodulin lead to rare autosomal dominant diseases, collectively referred to as uromodulin-associated kidney diseases. They are characterized by progressive tubulointerstitial damage, impaired urinary concentrating ability, hyperuricemia, renal cysts, and progressive renal failure. Novel in vivo studies point at intracellular accumulation of mutant uromodulin as a key primary event in the disease pathogenesis. Recently, genome-wide association studies identified uromodulin as a risk factor for chronic kidney disease (CKD) and hypertension, and suggested that the level of uromodulin in the urine could represent a useful biomarker for the development of CKD.

[Undercarboxylated osteocalcin (Glu-OC) bone metabolism and vascular calcification in hemodialyzed patients]. / Niedokarboksylowana osteokalcyna (Glu-OC) a metabolizm kostny i kalcyfikacja naczyn u chorych hemodializowanych.

UNLABELLED: Osteocalcin (OC) is witamino-K dependent calcium-binding protein comprising three gamma carboxy glutamic acid residues (Gla) which determines a strong bond with hydroxyapatite. In vitamin K deficiency and/or increased bone resorption undercarboxylated osteocalcin (Glu-OC) appears in the blood. The aim of this study was to evaluate the level of Glu-OC and markers of bone metabolism and their impact on coronary artery calcification in patients with end-stage renal failure treated with repeated hemodialysis. The study included 68 patients (29 women and 39 men) aged 60.3 +/- 12.3 years hemodialysis period 24.5 +/- 4.8 months. Control group consisted of 35 healthy volunteers comparable in terms of age and gender. CACS was evaluated based on multislice spiral computed tomography (MSCT). Measurement of carboxylated osteocalcin (Gla-OC) and Glu-OC, bone alkaline phosphatase (bALP), tartrate-resistant acid phosphatase (TRAP5) were assessed by ELISA and iPTH by Nichols method. Present study demonstrated that the Gla-OC and Glu-OC in hemodialysis patients were significantly higher than the control group 116.37 +/- 70.01 ng/ml and 93.72 +/- 112.63 ng/ml versus 19.51 +/- 3.78 ng/ml and 4.88 +/- 2.63 ng/ ml; p <0.001. Glu-OC level correlated significantly with iPTH, bALP, TRAP5 (p <0.001) and CaSc (p <0.014). CONCLUSIONS: 1. The results indicate a significant correlation between Glu-OC and assessed markers of bone metabolism. 2. Research has indicated a link between bone metabolism and the degree of calcification in the coronary arteries.

[The relationship between serum soluble apoptosis marker (sTRAIL) concentration and nutritional parameters in hemodialyzed patients]. / Zaleznosc pomiedzy stezeniem w surowicy rozpuszczalnego markera apoptozy (sTRAIL) a wskaznikami odzywienia u chorych hemodializowanych.

UNLABELLED: TRAIL (TNF-related apoptosis-inducing ligand) acts as a soluble cytokine interacting with transmembrane receptors belonging to the TNF-receptor family. TRAIL can activate both apoptotic and anti-apoptotic signals. Lower levels of serum sTRAIL were inversely associated with a higher risk of all-cause mortality in CKD population. A strong association between malnutrition, inflammation and atherosclerosis, have been observed in CKD patients. The aim of the study was to investigate the relationship between sTRAIL and nutritional markers and adipose tissue metabolism indices in patients on maintenance hemodialysis. The study was performed in group of 76 patients (36 female and 40 male) of average age 60 +/- 12 years on hemodialysis (74.8 +/- 58.0 months). sTRAIL, leptin and adiponectin were determined by ELISA, BMI based on Quetelet formula and serum albumin level using colorimetric bromokrezol green method. The following values of studied parameters were obtained: sTRAIL = 959.6 +/- 204.0 pg/ml, BMI = 24.5 +/- 4.8, leptin = 36.42 +/- 57.94 ng/ml, adiponectin = 17.55 +/- 10.52 microg/ml, leptin/ adiponectin (x10(-3)) = 2.1 +/- 4.5 and albumin = 38.5 +/- 4.5 g/l. sTRAIL correlate negatively with adiponectin and positively with the remaining studied parameters: BMI, albumin, leptin and leptin/adiponectin ratio. CONCLUSION: The observed interrelations between sTRAIL and nutritional parameters as well as studied adipokines may indicate the modulating role of sTRAIL in metabolic regulation.

Imaging of inflamed carotid artery atherosclerotic plaques with the use of 99mTc-HYNIC-IL-2 scintigraphy in end-stage renal disease patients.

PURPOSE: Identification of vulnerable plaques remains crucial for better cardiovascular risk assessment. At least 20% of inflammatory cells within unstable (vulnerable) plaques comprise T lymphocytes, which contain receptors for interleukin-2 (IL-2); those receptors can be identified by scintigraphy with radiolabelled IL-2.The aim of this study was to identify the "inflamed" (vulnerable) plaques by scintigraphy using IL-2 labelled with (99m)Tc in the selected, high cardiovascular risk group of end-stage renal disease (ESRD) patients. METHODS: A total of 28 patients (18 men, 10 women, aged 55.2 ± 9.6 years, 17 on peritoneal dialysis, 11 on haemodialysis) underwent common carotid artery (CCA) scintigraphy with the use of (99m)Tc-hydrazinonicotinamide (HYNIC)-IL-2. In all cases, ultrasound examination of the CCA was performed and levels of selected proinflammatory factors, atherogenic markers and calcium-phosphate balance parameters were measured. Finally, the target to non-target (T/nT) ratio of IL-2 uptake in atherosclerotic plaques with intima-media thickness (IMT), classic cardiovascular risk factors and concentrations of the measured factors were compared. RESULTS: Increased (99m)Tc-HYNIC-IL-2 uptake in atherosclerotic plaques in 38/41 (91%) cases was detected. The median T/nT ratio of focal (99m)Tc-HYNIC-IL-2 uptake in atherosclerotic plaques was 2.35 (range 1.23-3.63). The mean IMT value on the side of plaques assessed by scintigraphy was 0.79 ± 0.18 mm (median 0.8, range 0.5-1.275). Correlations between T/nT ratio and homocysteine (R = 0.22, p = 0.037), apolipoprotein B (apoB) (R = 0.31, p = 0.008), apoB to apoA-I ratio (R = 0.29, p = 0.012) and triglyceride concentration (R = 0.26, p = 0.021) were detected. A lower T/nT ratio in patients with better parameters of nutritional status (haemoglobin, albumin, adiponectin) in comparison with patients with worse nutritional parameters (3.20 ± 0.5 vs 2.16 ± 0.68, p = 0.025) was revealed as well as a difference between values of T/nT ratio in groups of patients with values of apoB, soluble CD40 ligand and asymmetric dimethylarginine above and below median (3.18 ± 0.52 vs 2.16 ± 0.68, p = 0.031). No statistically significant association was found between T/nT ratio and mean value of either IMT or classic cardiovascular risk factors. CONCLUSION: Scintigraphy with the use of (99m)Tc-HYNIC-IL-2 can be a tool for inflamed atherosclerotic (vulnerable) plaque visualization within CCA in ESRD patients. Quantitative results of carotid artery scintigraphy with (99m)Tc-HYNIC-IL-2 correlate with serum concentration of selected cardiovascular risk markers.

[Oxidative stress and its significance in prostate diseases]. / Stres oksydacyjny i jego rola w chorobach gruczolu krokowego.

The disturbed balance between production of reactive oxygen and nitrogen species (RONS) and efficiency of antioxydative systems leads to oxidative stress. This may be the cause of permanent biomolecules' damage. The results of many researches show dependence between disturbance in oxidative balance. And oxidative damage in prostate cells. However no clear evidence have been found that oxidative stress may lead to development of prostate cancer.

Serum matrix Gla protein concentrations in patients with mild and severe acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) causes an increase in proinflammatory cytokine and acute phase protein levels. Our previous studies in AP showed the role of fetuin A as a negative acute phase protein. Matrix Gla protein (MGP), beside fetuin A, is one of the main inhibitors of extraosseous calcification. In the present preliminary study we evaluated the relationship between MGP, lipase, and inflammation in AP patients. METHODS: The study included 40 patients with AP of diverse severity (28 mild, 12 severe), assessed during the early phase of AP (day 1 - day 7 of hospitalization). The concentration of MGP, fetuin A, polymorphonuclear elastase (PMN-elastase), interleukin 6 (IL-6), interleukin 18 (IL-18), hepatocyte growth factor (HGF), high sensitivity tumor necrosis factor alpha (hs TNFalpha), soluble receptor of tumor necrosis factor II (sTNFRII), and neopterin were measured by ELISA kits; albumin, lipase and amylase were measured on a Modular P Chemistry Analyser (Roche Diagnostica, Germany); procalcitonin (PCT) was measured using the LUMItest PCT (Brahms, Germany), and serum amyloid A (SAA) and high sensitivity C-reactive protein (hs CRP) were measured using an immunonephelometric method on a Nephelometer BNII (Siemens Healthcare, Germany). RESULTS: MGP positively correlated with lipase activity (R = 0.64; p < 0.05) on day 1 after admission to hospital. Lower MGP levels were consistent with higher intensity of inflammation, as MGP significantly (p < 0.05) inversely correlated with IL-6 (R = -0.48 on day 3; R = -0.46 on day 5 and R = -0.52 on day 7 after admission), IL-18 (R = - 0.55; R = -0.60; R = -0.48 on day 1, day 3, and day 5, respectively), HGF (R = -0.58 on day 3), hs TNFalpha (R = -0.45 on day 1 and R = -0.64 on day 5), its soluble receptor sTNFRII (R = -0.63; R = -0.61; R = -0.59 on day 3, day 5, and day 7, respectively), hs CRP (R = -0.76 on day 1 and R = -0.83 on day 5), PCT (R = -0.62 on day 1 and R = -0.59 on day 7), SAA (R = -0.45 on day 5) as well as with neopterin (R = -0.52 on day 1 after admission). MGP levels dropped simultaneously with fetuin A (R = 0.50 on day 3; R = 0.60 on day 5 and R = 0.63 on day 7) and albumin concentrations (R = 0.51; R = 0.70; R = 0.94 on day 1, day 5, and day 7 day after admission, respectively). There was a relationship between lipase activity and MGP concentration on day 1 of hospitalization (R = 0.64; p < 0.05). CONCLUSIONS: Our preliminary results indicate that the MGP level correlated negatively with all of the proinflammatory cytokines and acute phase proteins studied in patients with AP, and positively with lipase, fetuin A, and albumin measurements. These findings may indicate the role of MGP in calcium and phosphate metabolism disturbances in the course of AP.

[Fibroblast growth factor-23 (FGF-23). Part I. Significance in phosphate homeostasis and bone metabolism]. / Czynnik wzrostu fibroblastów-23 (FGF-23). Czesc I. Znaczenie w homeostazie fosforanowej i metabolizmie kostnym.

Fibroblast growth factor-23 (FGF-23) discovered in the last years, produced by osteocytes and osteoblast is hormone that lowers plasma phosphate level due to inhibition of renal tubule phosphate reabsorption (phosphaturic effect). It diminishes gut absorption of phosphate as a result of lowered kidney 1alpha-hydroxylase activity and respective decreased active vitamin D1,25(OH)2D synthesis. FGF-23 acts in the presence of the co-receptor Klotho protein which stabilizes its binding with receptor. The pathological states that are associated with increased FGF-23 synthesis in normal renal function lead to hypophosphatemia, while its deficiency may lead to severe hyperphosphatemia. The increased FGF-23 synthesis in patients with chronic kidney disease (CKD) allow to maintain phosphate concentration in spite of severe kidney dysfunction. This problem will be discussed in the II-nd part of this review.

[Fibroblast growth factor-23 (FGF-23). Part II. Significance in chronic kidney disease]. / Czynnik wzrostu fibroblastów-23 (FGF-23). Czesc II. Rola w przewleklej chorobie nerek.

Fibroblast growth factor-23 (FGF-23) is a phosphatonine of important value in maintenance of mineral homeostasis. In the 1st part of this review dealing with FGF-23 its composition, mode of action, and regulatory mechanisms of its secretion were described. In the 2nd part of this work, regulatory activity in the calcium-phosphate homeostasis in different stages of chronic kidney disease (CKD) with special attention to increased synthesis of FGF-23 in the course of declined glomerular filtration rate were elucidated. The FGF-23 concentration in dialyzed patients, subjects after parathyroidectomy and patients after kidney transplantation were characterized. The relationship between FGF-23 serum concentaration and cardiovascular morbidity and mortality will be presented in the 3rd part of this review.

[Fibroblast growth factor-23 (FGF-23). Part III. Relationship between FGF-23 serum concentration and cardio-vascular morbidity and mortality]. / Czynnik wzrostu fibroblastów-23 (FGF-23). Czesc III. Zaleznosci pomiedzy stezeniem FGF-23 a chorobowoscia i smiertelnoscia sercowo-naczyniowa.

In the 1st part of this review dealing with FGF-23 its composition, mode of action, and regulatory mechanisms of its secretion were described. In the 2nd part of this review, regulatory activity in the calcium-phosphate homeo-stasis in different stages of chronic kidney disease (CKD) including dialyzed patients, subjects after parathyreoidectomy and patients after kidney transplantation were characterized. The aim of this part was to analyze the relationship between FGF-23 and left ventricular hypertrophy, vascular calcification and increased morbidity and mortality in patients with CKD. The current knowledge on FGF-23 has lead to suspect that in the nearest future it may serve as sensitive marker of early calcium-phosphate disturbances in patients with CKD.