Monte Carlo simulations and experimental results on neutron production in the uranium spallation target QUINTA irradiated with 660 MeV protons.

The activation experiment was performed using the accelerated beam of Phasotron accelerator at the Joint Institute for Nuclear Research (JINR). The natural uranium spallation target QUINTA was irradiated with protons with energy 660 MeV. Monte Carlo simulations of neutron production were performed using the Geant4 code. The number of leakage neutrons from the sections of the uranium target surrounded by the lead shielding and the number of leakage neutrons from lead were determined. The total number of fissions in the setup QUINTA was determined. Experimental values of reaction rates for the produced nuclei in the 127I sample were obtained and several values of reaction rates were compared with the results of simulations. Experimentally determined fluence of neutrons in energy interval 10-175 MeV using the (n,xn) reactions in the 127I(NaI) sample was compared with the results of simulations. Possibility of transmutation of the long-lived radionuclide 129I in the QUINTA setup was estimated.

Study of secondary neutron interactions with ²³²Th, ¹²9I, and ¹²7I nuclei with the uranium assembly "QUINTA" at 2, 4, and 8 GeV deuteron beams of the JINR Nuclotron accelerator.

The natural uranium assembly, "QUINTA", was irradiated with 2, 4, and 8GeV deuterons. The (232)Th, (127)I, and (129)I samples have been exposed to secondary neutrons produced in the assembly at a 20-cm radial distance from the deuteron beam axis. The spectra of gamma rays emitted by the activated (232)Th, (127)I, and (129)I samples have been analyzed and several tens of product nuclei have been identified. For each of those products, neutron-induced reaction rates have been determined. The transmutation power for the (129)I samples is estimated. Experimental results were compared to those calculated with well-known stochastic and deterministic codes.

[HE4 a biomarker of ovarian cancer]. / HE4 - biomarker ovariálního karcinomu.

OBJECTIVE: Verification of the importance of determination of HE4 and calculation of ROMA index for increasing the efficiency of diagnosis of ovarian cancer in a population of Czech women. DESIGN: Prospective study. SETTING: Department of Gynaecology and Obstetrics, Faculty Hospital in Pilsen. METHODS: In the period from 06/24/2010 to 12/01/2011 was at the Department of Gynaecology and Obstetrics, University Hospital Pilsen examined 552 patients with abnormalities in the pelvis. Patients were divided into two groups. There were 30 women with histologically confirmed malignant ovarian tumors. Another 522 women had benign findings. According to the levels of FSH were women in both groups divided into premenopausal and postmenopausal. At all women were measured CA 125, HE4 and FSH. HE4 and CA125 were determined using the chemiluminescent device Architect 1000 (Abbott, USA), FSH chemiluminescent method on the device DXI 800 (Beckman Coulter, USA). At all premenopausal women was calculated ROMA1 index and at all postmenopausal women ROMA2 index. SAS statistical software 9.2 were used for all statistical calculations. RESULTS: The highest diagnostic efficiency was achieved by a combination of HE4 and CA125 markers with the calculation ROMA2 index for postmenopausal women. In determining of menopausal status according to the values of FSH cut-off for menopause 40 IU/L and cut-off at 26.4% for ROMA2 reaches ROMA2 sensitivity of 92.3%, specificity of 88.5% and PV- of 99.3%. If we reduce the cut-off for laboratory diagnosis of menopause using FSH at 22 IU/L, and cut-off for ROMA2 was 26.3% reaches ROMA2 sensitivity of 95.2%, specificity of 87.8% and PV- of 99.5%. CONCLUSION: HE4 in combination with CA125 and current ROMA index calculation is a suitable methodology to improve the detection of ovarian cancer.

Matrix metalloproteinases and their inhibitors in correlation to proliferative and classical tumour markers during surgical therapy of colorectal liver metastases.

OBJECTIVES: Classical and proliferative tumour markers and matrix metalloproteinases and their tissue inhibitors reflect the features of malignancy and are useful in prediction of prognosis in patients with colorectal liver metastases. There is very limited information about their physiological functions during regeneration and healing of liver parenchyma after any type of liver surgery for malignancy. METHODS: The presented study included the patients, who underwent following surgical procedures for CLM, benign liver lesions and inguinal hernias: Group A: 22 patients with inguinal hernias, Group B: 26 patients with benign liver lesions, Group C: 30 patients with colorectal liver metastases (CLM) who were treated by radiofrequency ablation, Group D: 41 patients with CLM who underwent a radical surgical therapy - resection, and Group E: 22 patients with inoperable CLM who underwent an explorative laparotomy without any surgical procedure. RESULTS: The preoperative and postoperative serum levels of CEA, CA 19-9, TK, TPA, TPS, MMP-2, MMP-9, TIMP-1, and TIMP-2 were statistically analyzed and compared within the groups to estimate the influence of a surgical procedure type. These results reflect the influence of surgical procedure on the serum levels of studied tumour markers during operation. CONCLUSIONS: It was the first description using these types of comparison to all metalloproteinases, their inhibitors, and proliferative and classical tumour markers. It could help us to estimate the critical relations of these tumour markers in prognoses of disease free survival or overall survival in patients after a surgical procedure for CLM (Tab. 5, Ref. 26).

The association between low 25-hydroxyvitamin D and increased aortic stiffness.

There is accumulating evidence that vitamin D exerts important pathophysiological effects on cardiovascular system. Low vitamin D was associated with increased cardiovascular risk in several reports. We studied the association between vitamin D and arterial stiffness in a random sample of 560 subjects selected from general population. Arterial stiffness was measured as aortic pulse-wave velocity (PWV) using Sphygmocor device. Serum 25-hydroxyvitamin D (25(OH)D) was measured using commercial kits. We found a clear negative trend in aortic PWV among 25(OH)D quartiles. Subjects in the bottom 25(OH)D quartile (<20 ng ml(-1)) showed the highest aortic PWV (9.04 m s(-1)), compared with 2nd-4th quartile (8.07 m s(-1), 7.93 m s(-1) and 7.70 m s(-1), respectively; P for trend <0.0001). The association between 25(OH)D and aortic PWV remained significant after adjustment for age, gender and other potential confounders; subjects in the first 25(OH)D quartile had adjusted odds ratio 2.04 (1.26-3.30) for having aortic PWV ≥9 m s(-1) (top quartile) in multiple regression. In conclusion, we found a clear significant and independent negative association between 25(OH)D and aortic PWV. Subjects with lowest vitamin D status showed the highest arterial stiffness.

[Can tumor markers predict outcomes of portal vein branch embolization in patients with primary inoperable liver tumors?]. / Mohou nádorové markery predpovídat výsledek embolizace vetve portální zíly u nemocných s primárne inoperabilním nádorem jater?

INTRODUCTION: Portal vein embolization (PVE) is one of the options to increase the number of resecable cases in patients with primary inoperable liver tumors. However, insufficient growth of liver parenchyma or postoperative tumor progression remains problematic in PVE procedures. Generally, tumor markers are of significance in patient postoperative monitoring for the disease recurrence. The aim of this study is to assess the potential of tumor markers in predicting PVE outcomes. METHOD: The study group included 43 subjects with primary or secondary tumors, in whom serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), thymidine kinase (TK), tissue polypetide antigen (TPS) and MonoTotal levels were assessed 28 days following PVE. The liver parenchyma growth or tumor progression were assessed based on computer tomography. RESULTS: Sufficient liver parenchyma hypertrophy was recorded in 27 (62.8 %) patients with subsequent liver resection. Insufficient post-PVE liver parenchyma growth was recorded in 5 (11.6 %) patients and tumor progression was recorded in 11 (25.6 %) subjects. The following tests were considered significant predictive tumor markers of PVE outcomes: serum levels of CEA, TPA, Mono Total prior to PVE, and serum levels of TK, TPA, Mono Total within 28 days following PVE. CONCLUSION: Tumor markers may be significant in predicting PVE outcomes in patients with primary inoperable liver tumors. However, in order to make final conclusions on their clinical significance, larger patient group studies should be performed.

[Plasmatic levels of proinflammatory cytokines in abdominal aortic aneurysms]. / Plazmatické hladiny prozánetlivých cytokinu u aneuryzmatu abdominální aorty.

INTRODUCTION: Inflammation within the abdominal aortic wall is generally considered a very significant ethiopathogenic factor in the development of abdominal aortic aneurysms. Proinflammatory cytokines are important mediators of inflammation within the abdominal aortic wall. AIM: The aim of the study was to research, whether plasmatic levels of certain proinflammatory cytokines, which can commonly be evaluated (TNFalpha, IL-1, -2, -6 a -8), play a significant role in the development of AAA. METHOD: The prospective non-randomized study included 345 patients with AAAs. The patients were assigned to 5 subgroups based on their symptoms and AAA diameters. The first subgroup included patients with symptomatic AAAs, including AAA ruptures (N = 69), the second subgroup included subjects with asymptomatic AAAs (N = 276) with AAA diameters up to 5 cm (N = 72), the third subgroup included 5 cm (N = 72), the fourth included 5-8 cm (N = 192) and the fifth subgroup included subjects with AAA diameters of more than 8 cm (N = 81). The mean age of patients was 74.1 +/- 7.8 years (56-84 y.o.a.). The male to female ratio was 5:1. The control group included 30 healthy volunteer subjects of similar age and male to female rates, who had no clinical signs of arterial disorders. Plasmatic levels of cytokines were evaluated from venous blood samples using ELISA (Bender, Austria) testing. Statistical assessment of the results was performed using ANOVA and Wilcoxon tests with Spearman's correlation. P values < 0.05 were considered significant. RESULTS: Plasmatic concentrations of proinflammatory cytokines were found to be statistically significantly higher in patients with AAAs compared to those in healthy volunteers. Plasmatic IL8 levels were significantly decreasing proportionally to decreasing AAA diameters (p < 0.05). TNFalpha levels were found to be significantly low in symptomatic patients with AAA ruptures (p < 0.05). CONCLUSION: The study confirmed the significance of proinflammatory cytokines levels monitoring in AAA patients. The authors showed that, for instance IL8 activity and to a certain extent TNFalpha activity, is the highest in small and developing AAAs. These findings would be significant for customized medication therapy aimed at blocking the effects of these factors on the inflammatory process within the AAA wall.

An inverse association between serum leptin concentration and reported alcohol intake in patients with manifest vascular disease.

BACKGROUND/OBJECTIVES: It has been reported that alcohol stimulates appetite. We aimed to establish the association between leptin, as a major food intake regulating factor, and alcohol intake in patients with chronic manifest coronary artery or cerebrovascular disease. SUBJECTS/METHODS: A cross-sectional study of 820 subjects after acute coronary syndrome, coronary revascularization or after first ischemic stroke (the Czech part of EUROASPIRE III surveys). Leptin concentrations were evaluated among predefined categories of reported weekly alcohol intake: abstainers, light drinkers (up to 2 drinks weekly, 1-44 g of pure alcohol), mild regular drinkers (3-14 drinks weekly, 45-308 g) and moderate or heavy drinkers (more than 15 drinks, ≥ 309 g of alcohol). RESULTS: Leptin showed a clear negative trend among the alcohol intake categories. Mild regular drinkers showed significantly lower leptin levels (9.3(8.2) ng/ml) compared with abstainers (18.7(18.7) ng/ml, P<0.0001) and light occasional drinkers (14.2(17.8) ng/ml, P=0.00064). The negative association between leptin and alcohol intake as a dependent variable remained significant even after adjustment for potential confounders in multiple linear regression analysis (P=0.00032). CONCLUSIONS: Drinking of small amounts of alcohol was, in our setting, associated with decreased serum leptin concentration, with a possible benefit in terms of cardiovascular risk.

Lower serum levels of interleukin-6 in a population sample with symptoms of depression than in a population sample without symptoms of depression.

In this study we compared the levels of interleukin (IL)-6, IL-8, IL-10 and tumor necrosis factor-alpha (TNF-alpha) in population samples characterized by a high or low level of self-reported depression. We measured serum IL-6, IL-8, IL-10 and TNF-alpha in two cohorts which differed in scoring on the Zung Self-Rating Depression Scale (ZSDS). The group with a high score in ZSDS (average SDS index = 62.9) was called DEP (n=27), the group with a low score in ZSDS (average SDS index = 29.9) was called NDEP (n=16). The groups did not significantly differ in age, waist circumference and body mass index. For the assessment of serum cytokine levels multiplex immunoanalytic xMAP(LUMINEX) technology was used. We found lower IL-6 in the DEP group (medians; DEP 4.08 pg/ml vs. NDEP 6.11 pg/ml) on the border of statistical significance in multiple regression analysis (p=0.049). Serum levels of all other studied cytokines were not significantly different (medians; IL-8: DEP 2.18 pg/ml vs. NDEP 2.61 pg/ml; IL-10: DEP 2.85 pg/ml vs. NDEP 2.94 pg/ml; TNF-alpha: DEP 2.32 pg/ml vs. NDEP 2.30 pg/ml). These results are in contradiction to the prevailing opinion that pro-inflammatory cytokine levels are elevated in people with symptoms of depression.

Significance of methylation status and the expression of RECK mRNA in lung tissue of patients with NSCLC.

OBJECTIVES: RECK (reversion-inducing cysteine-rich protein with Kazal motifs) is a glycoprotein which negatively regulates the activity of matrix metalloproteinases (MMPs). We analyzed differences in RECK mRNA expression in histological types of non-small cell lung cancer (NSCLC) and the relationship between promoter methylation status of RECK gene, level of RECK mRNA expression and clinicopathological values of patients with NSCLC. PATIENTS AND METHODS: Methylation status of the promoter and the expression of RECK mRNA were analyzed in paired tissue samples (tumor and control) of 50 patients with NSCLC. The methylation status of the RECK promoter was assessed using methylation-specific PCR. The level of RECK mRNA expression was measured using an RT real-time PCR method. RESULTS: Lower expression of RECK mRNA in NSCLC tissue was recorded compared to normal tissue (p=0.0032). Significantly lower expression of RECK in squamous cell carcinoma (SCC) tissue was observed in comparison with adenocarcinoma tissue (p=0.0051). Significant differences in expression of RECK in stages IB-IIIA were found in comparison with stage IA (p=0.0455). There was a significantly lower expression of RECK mRNA in NSCLC tissue in samples with positive RECK promoter methylation status in comparison with samples with negative promoter methylation status (p=0.0400). CONCLUSION: We showed that there were differences in expression between histological types of NSCLC (SCC, adenocarcinoma). There was a higher expression of RECK in stage IA in comparison with stages IB-IIIA. Our results indicate that RECK could be classified as a tumor suppressor gene and is an interesting target for further investigation of MMP inhibitors.

Expression of MMP-7, MMP-9, TIMP-1 and TIMP-2 mRNA in lung tissue of patients with non-small cell lung cancer (NSCLC) and benign pulmonary disease.

UNLABELLED: The expression of matrix metallo-proteinases (MMP-7 and MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), which are involved in the degradation of the extracellular matrix (ECM) and tumor growth, was investigated in normal lung tissue, tissue of benign pulmonary diseases and non-small cell lung cancer (NSCLC) tissue. PATIENTS AND METHODS: Tumor tissue and surrounding carcinoma-free lung tissue samples were obtained from 91 patients with NSCLC who had undergone surgery in the years 2005-2007 as well as lung tissue from 12 patients operated on for 'benign' bullous emphysema or interstitial lung disease. The mRNA was isolated from the tissues and the expression of mRNA was assessed using a real-time RT PCR method. RESULTS: Significantly higher expression of MMP-7, MMP-9 and TIMP-1 mRNA was demonstrated in the NSCLC tissue in comparison with the normal lung tissue from the same patients (p=0.0003, p<0.0001 and p=0.0018, respectively). Similar results for MMP-7, MMP-9 and TIMP-1 were found in the histological subgroups: squamous cell lung cancer vs. normal tissue (p=0.0198, p=0.0015 and p=0.0366, respectively), and adenocarcinoma vs. normal tissue (p=0.0045, p<0.0001 and p=0.0140, respectively). The expression of MMP-7 was found to be significantly higher in tumor tissue vs. lung tissue of the benign diseases (p=0.0086) and similar results were also recorded in the histological subgroups: squamous cell lung cancer vs. benign tissue (p=0.0171) and adenocarcinoma vs. benign tissue (p=0.0135). The expression of MMP-9 was significantly higher only in the adenocarcinoma subgroup vs. the benign tissue (p=0.0412). No differences in the expression of mRNA between stage IA and stages IB-IIIB of NSCLC were recorded. CONCLUSION: Significantly higher expression of MMP-7 and MMP-9 in tumor tissue than in the surrounding tissue or in benign lung disease tissue supports the notion of an important role of these metalloproteinases in the growth of lung carcinoma. TIMP-1 expression is increased only in carcinoma, but not in benign lung disease.