Distinct Expression Patterns of Two Tumor Necrosis Factor Superfamily Member 15 Gene Isoforms in Human Colon Cancer.

BACKGROUND: Tumor necrosis factor superfamily member 15 (TNFSF15) gene is involved in development of several cancers. It encodes two proteins: tumor necrosis factor ligand-related molecule 1A (TL1A) and vascular endothelial growth inhibitor 192 (VEGI-192). The main receptor for TL1A is death receptor 3 (DR3). AIMS: We investigated expression of TL1A, VEGI-192, and DR3 transcripts in different stages of colon cancer and compared them with survival of patients. We also aimed to reveal possible effects of microsatellite instability (MSI) and selected TNFSF15 single-nucleotide polymorphisms (SNPs) on expression of this gene. METHODS: Forty-five healthy individuals and 95 colon cancer patients were included in the study. Expression of VEGI-192, TL1A, and DR3 was measured by quantitative PCR. SNP and MSI analyses were performed on DNA isolated from normal or cancer tissue. RESULTS: Expression of VEGI-192 and TL1A was elevated in colon cancer, although the level of VEGI-192 decreased, while the level of TL1A increased with the progression of cancer. Patients with low expression of TL1A and/or high expression of VEGI-192 in tumor-transformed tissue showed longer survival. DR3 expression was decreased in the cancer, but it did not change with the tumor progression. Alleles T of rs6478108 and G of rs6478109 SNPs were associated with elevated expression of the TNFSF15 gene. There was no relation between the MSI status and TNFSF15 expression levels. CONCLUSIONS: Expression of the TNFSF15 gene isoforms was associated with the progression of colon cancer. Levels of TL1A and VEGI-192 transcripts can be considered as independent prognostic factors for colon cancer.

Inverse association of serum bilirubin with metabolic syndrome and insulin resistance in Polish population.

BACKGROUND: Bilirubin has got a potential anti-oxidant, anti-inflammatory and cytoprotective effect. It has been shown that its concentration is inversely related to cardiometabolic diseases. Recent studies have revealed the association between serum bilirubin concentrations and metabolic syndrome (MS) among children and adolescents in U.S. and among Korean adults. The aim of this study was to evaluate the association of total serum bilirubin level with MS and insulin resistance in Poland. METHODS: We examined 1568 patients aged 18 to 93 years. The tested population was a nationally representative sample of Polish adults. They were derived from cross-sectional study, when serum total bilirubin level and risk factors of cardiovascular diseases were determined. RESULTS: The prevalence of MS in bilirubin level quartiles (95% CI in parentheses) was 28.9% (24.5%-33.3%), 32.6% (28.3%-36.9%), 23.4% (19.0%-27.8%), 21.8% (17.5%-26.2%) respectively for quartiles 1-4 (p = 0.002) The multivariate analysis showed odds ratio for MS in third and fourth quartile of bilirubin level equal to 0.70 (0.50-0.99) and 0.68 (0.48-0.95) respectively in comparison to the lowest quartile. The more criteria of metabolic syndrome were fulfilled by the patient, the lower was mean total bilirubin level (p = 0.012). In study group there was also a strong, independent association of bilirubin level with fasting insulin level and insulin resistance (HOMA-IR). The odds ratio of insulin resistance was 0.53 (0.38-0.74) for the fourth quartile in reference to the lowest quartile of bilirubin. CONCLUSION: In Polish adults serum total bilirubin level is inversely related to the prevalence of MS and insulin resistance.

Expanded Role of a Dietitian in Monitoring a Gluten-Free Diet in Patients with Celiac Disease: Implications for Clinical Practice.

Access to a registered dietitian experienced in celiac disease (CD) is still limited, and consultation when available focuses primarily on the elimination of gluten from the diet. Thus, the aim of this study was to evaluate the nutritional value of a gluten-free diet (GFD) in adult CD patients before, and one year after, the standard dietary education. The study included 72 CD patients on a GFD and 30 healthy controls. The dietary intake of both groups was assessed through a 3-day food diary, while adherence to a GFD in celiac subjects was assessed using Standardized Dietician Evaluation (SDE). Subsequently, all CD patients received detailed education on gluten sources, and 48 of them participated in a one-year follow-up. Results: Comparison with the control group showed that consumption of plant protein in CD patients was significantly lower, whereas fat and calories were higher. At baseline, only 62% of CD patients adhered to a GFD, but the standard dietary education successfully improved it. However, the nutritional value of a GFD after one year did not change, except for a reduced sodium intake. The CD subjects still did not consume enough calcium, iron, vitamin D, folic acid or fiber. In conclusion, while the standard dietary education improved GFD adherence, it did not significantly alter its nutritional value. Therefore, it is necessary to increase the role of a dietitian in the treatment of CD.

Adipose tissue activity in relation to overweight or obesity.

INTRODUCTION: Obesity is associated with a number of diseases resulting from the excessive amount of adipose tissue. The aim of this study was to investigate the correlation between the quantity of adipose tissue and the prevalence of metabolic disturbances, and the concentration of adipokines and proinflammatory cytokines in obese or overweight patients. MATERIAL AND METHODS: Fifty-five middle-aged subjects with body mass index (BMI) > 25 kg/m(2) took part in this study. Twenty-three healthy people with normal BMI formed the control group. Twenty-one people from the study group were on a low-calorie diet. All subjects underwent anthropometric assessment, laboratory investigations, and blood-pressure examination. RESULTS: Patients with obesity or overweight, in comparison to those with normal BMI, showed insulin resistance and a higher concentration of high sensitivity C-reactive protein (hs-CRP), plasminogen activator inhibitor 1 (PAI-1), and interleukin 6 (Il-6). The concentration of adiponectin was significantly lower in this group. The patients on the low-calorie diet had significantly lower concentrations of leptin when compared to other obese people; moreover, a trend towards decreased hs-CRP concentration was seen. A significant positive correlation between leptin and hs-CRP was observed. The serum concentration of adiponectin was inversely correlated with that of TNF-alpha, IL-6, hs-CRP, and PAI-1. CONCLUSIONS: The results of this study may suggest the beneficial impact of a low-calorie diet on the slowing down of inflammatory processes. The observed negative correlation between the concentrations of adiponectin and inflammatory cytokines may confirm the anti-inflammatory activity of this adipokine.

Celiac Dietary Adherence Test and Standardized Dietician Evaluation in Assessment of Adherence to a Gluten-Free Diet in Patients with Celiac Disease.

Adherence to a gluten-free diet (GFD) is currently the mainstay of treatment strategy for celiac disease (CD). The aim of our study was measuring a GFD adherence in CD patients using two newly validated methods of dietary assessment-Standardized Dietician Evaluation (SDE) and the Celiac Dietary Adherence Test (CDAT). Ninety-two adults with CD were evaluated by a registered dietitian with extensive experience with the use of SDE and CDAT. Duodenal biopsy was performed and blood was drawn for serum anti-endomysial, anti-deamidated gliadin peptide and anti-tissue transglutaminase antibodies in forty four of those patients. The results of CDAT and SDE were very convergent, but SDE scores better correlated with serologic and histologic findings. As many as 24-52% of study participants did not adhere well enough to a GFD. Insufficient adherence to a GFD in CD patients is still a significant problem. The knowledge about gluten content in food ingredients and additives is very low among adults with CD. SDE is the most accurate method in assessing compliance with a GFD and is especially helpful in determining hidden sources of gluten. The CDAT may be a fast tool for screening for a GFD adherence in CD patients.

FasR and FasL in colorectal cancer.

Colorectal cancer (CRC) is one of the most common solid organ cancers prevalent worldwide causing, in spite of advancing therapeutic methodology, high rate of patient mortality, especially due to metastasis development. The cancer stem cell (CSC) theory of tumor growth indicates that CSCs within the tumor mass have great capacity to initiate and sustain tumor growth. Following the suggestion that Fas signaling can be engaged in apoptosis, tumor maintenance, senescence or DICE (death induced by CD95 or CD95L elimination), the attempts to broaden the knowledge concerning the relationships between CSCs features and FasR/FasL appeared to be necessary. The most important advantage of our study was the simultaneously analysis of CSCs from commonly used CRC lines (HCT116 and HT29) and tumor fragments collected from CRC patients. Moreover, the sphere-promoting expansion of CRC lines brought a specific three-dimensional specific environment for CSC exploration. We further investigated the function of Fas signaling in CRC lines depending on the culture mode as we incubated HCT116 and HT29 cells with anti-FasR agonistic antibodies. It appeared to act in a line-dependent and culture mode-dependent manner and influenced some particular features of CSCs such as spherogenicity, proliferation and phenotype. Additionally, the analysis of mRNA level showed that disease progression is associated with significantly increased expression of FasR and/or FasL. In conclusion, our observation seems to confirm that spherical model of cancer lines is more reliable for some sophisticated analysis because of their greater resemblance to the CSCs from human CRC samples in comparison to commonly used adherent cells, at least according to aspects of their biology analyzed in this study. That can be extended to the resemblance of in vitro sphere forming conditions to the in vivo environment. However, the greatest difference concerns the level of apoptosis, thus, this issue require further experiments.

Heart rate variability (HRV) and muscular system activity (EMG) in cases of crash threat during simulated driving of a passenger car.

OBJECTIVES: The aim of the study was to verify whether simultaneous responses from the muscular and circulatory system occur in the driver's body under simulated conditions of a crash threat. MATERIALS AND METHODS: The study was carried out in a passenger car driving simulator. The crash was included in the driving test scenario developed in an urban setting. In the group of 22 young male subjects, two physiological signals - ECG and EMG were continuously recorded. The length of the RR interval in the ECG signal was assessed. A HRV analysis was performed in the time and frequency domains for 1-minute record segments at rest (seated position), during undisturbed driving as well as during and several minutes after the crash. For the left and right side muscles: m. trapezius (TR) and m. flexor digitorum superficialis (FDS), the EMG signal amplitude was determined. The percentage of maximal voluntary contraction (MVC) was compared during driving and during the crash. RESULTS: As for the ECG signal, it was found that in most of the drivers changes occurred in the parameter values reflecting HRV in the time domain. Significant changes were noted in the mean length of RR intervals (mRR). As for the EMG signal, the changes in the amplitude concerned the signal recorded from the FDS muscle. The changes in ECG and EMG were simultaneous in half of the cases. CONCLUSION: Such parameters as mRR (ECG signal) and FDS-L amplitude (EMG signal) were the responses to accident risk. Under simulated conditions, responses from the circulatory and musculoskeletal systems are not always simultaneous. The results indicate that a more complete driver's response to a crash in road traffic is obtained based on parallel recording of two physiological signals (ECG and EMG).

Sclerosing cholangitis associated with retroperitoneal fibrosis: a case of multisystem fibroinflammatory disorder.

INTRODUCTION: Retroperitoneal fibrosis is a fibroinflammatory disease of unknown etiology that can be associated with other fibroinflammatory disorders. Lately, there have been several reports showing that retroperitoneal fibrosis is a manifestation of IgG4-related sclerosing disease, which often presents as autoimmune pancreatitis. CASE REPORT: This report shows the case of IgG4-related sclerosing cholangitis associated with retroperitoneal fibrosis independent of autoimmune pancreatitis. The patient presented with cholestatic jaundice and picture of sclerosing cholangitis in endoscopic retrograde cholangiography. The combination of endoscopic biliary drainage and steroid therapy was an effective treatment in this case. CONCLUSION: The diagnosis of IgG4-related sclerosing disease should always be taken into consideration in patients with sclerosing cholangitis, especially when it is associated with any fibroinflammatory disorder.